Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer

Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways—neurotrophic factors (TrkB/BDNF) and autophagy—on cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages. On the basis of our previous study (which demonstrated that TrkB overexpression is associated with prosurvival signaling in CRC cells), we pharmacologically inhibited NTs pathways with K252a. As expected, an inactivation of the PI3K/AKT pathway was observed and CRC cells initiated autophagy. Conversely, blocking the autophagic flux with chloroquine or with ATG5‐siRNA overactivated TrkB/BDNF signaling. In vitro, dual inhibition improved the effectiveness of single treatment by significantly reducing metabolic activity and enhancing apoptotic cell death. These findings were accentuated in vivo, in which dual inhibition induced a spectacular reduction in tumour volume following long‐term treatment (21 days for K252a and 12 days for CQ). Finally, significant amounts of phospho‐TrkB and LC3II were found in the patients’ tissues, highlighting their relevance in CRC tumour biology. Taken together, our results show that targeting NTs and autophagy pathways potentially constitutes a new therapeutic approach for CRC.     

lncRNA HCG11 regulates cell progression by targeting miR‐543 and regulating AKT/mTOR pathway in prostate cancer

Prostate cancer (PCa) is a common cancer worldwide, which mostly occurs in males over the age of 50. Accumulating evidence have determined that long non‐coding RNA/microRNA (lncRNA/miRNA) axis plays a critical role in cell progression of cancers, including PCa. However, the pathogenesis of PCa has not been fully indicated. In this study, quantitative real‐time polymerase chain reaction was used to detect the expression of HCG11 and miR‐543. Western blot was applied to measure the protein expression of proliferating cell nuclear antigen, cleavage‐caspase 3 (cle‐caspase 3), N‐cadherin, E‐cadherin, GAPDH, P‐AKT, AKT, p‐mTOR, and mTOR. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), transwell invasion, and transwell migration assay were used to detect cell proliferation, invasion, and migration, respectively. The function and mechanism of lncRNA HCG11 were confirmed in PCa cell and xenograft mice models. Luciferase assay indicated that miR‐543 was a target miRNA of HCG11. Further investigation revealed that overexpression of HCG11 inhibited cell proliferation, invasion, and migration, whereas induced cell apoptosis by regulating miR‐543 expression in vitro and in vivo. More than that, lncRNA HCG11 inhibited phosphoinositide‐3 kinase/protein kinaseB (PI3K/AKT) signaling pathway to suppress PCa progression. Our data showed the overexpression of HGC11‐inhibited PI3K/AKT signaling pathway by downregulating miR‐543 expression, resulting in the suppression of cell growth in PCa. This finding proved a new regulatory network in PCa and provided a novel therapeutic target of PCa.     

Upregulated KDM4B promotes prostate cancer cell proliferation by activating autophagy

Castration-resistant prostate cancer (CRPC) causes most of the deaths in patients with prostate cancer (PCa). The androgen receptor (AR) axis plays an important role in castration resistance. Emerging studies showed that the lysine demethylase KDM4B is a key molecule in AR signaling and turnover, and autophagy plays an important role in CRPC. However, little is known about whether KDM4B promotes CRPC progression by regulating autophagy. Here we used an androgen-independent LNCaP (LNCaP-AI) cell line to assay aberrant KDM4B expression using qPCR and western blot analysis and investigated the function of KDM4B in regulating cell proliferation. We found that KDM4B was markedly increased in LNCaP-AI cells compared with LNCaP cells. KDM4B level was significantly correlated with the Gleason score in PCa tissues. In vitro, KDM4B overexpression in CRPC cells promoted cell proliferation, whereas knockdown of KDM4B significantly inhibited cell proliferation. Upregulated KDM4B contributed to activate Wnt/β-catenin signaling and autophagy. Moreover, KDM4B activated autophagy by regulating the Wnt/β-catenin signaling. Finally, we demonstrated that autophagy inhibition attenuated KDM4B-induced CRPC cell proliferation. Our results provided novel insights into the function of KDM4B-driven CRPC development and indicated that KDM4B may be served as a potential target for CRPC therapy.     

Ropivacaine inhibits proliferation and invasion and promotes apoptosis and autophagy in bladder cancer cells via inhibiting PI3K/AKT pathway

Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC) have never been explored. We explored the effects of ropivacaine on the progression of BC in vitro and in vivo. CCK8 assay and EDU staining was conducted to examine cell proliferation. Flow cytometry and transwell assay were performed to evaluate apoptosis and invasion, respectively. Expression of light chain 3 (LC3) was observed through immunofluorescence. Furthermore, the xenograft tumor model of BC was built to detect the effects of ropivacaine in vivo. IHC and TUNEL assay were conducted to detect cell proliferation and apoptosis in vivo. Ropivacaine inhibited the proliferation of T24 and 5639 cells with the 50% inhibitory concentration (IC50) of 20.08 and 31.86 µM, respectively. Ropivacaine suppressed the invasion ability and induces the apoptosis of cells. Besides, ropivacaine triggers obvious autophagy in BC cells. Moreover, ropivacaine blocks the PI3K/AKT signal pathway in BC cells. The impact of ropivacaine on cell viability, motility, and autophagy was reversed by 740 Y-P, the activator of PI3K/AKT signal pathway. The in vivo experiments demonstrated that ropivacaine inhibited the proliferation and mobility of BC. Ropivacaine has anti-carcinoma effects in BC via inactivating PI3K/AKT pathway, providing a new theoretical reference for the use of local anesthetics in the treatment of BC.     

The Notch pathway in prostate development and cancer

Abstract The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch signaling in normal prostate development. Notch signaling is required for embryonic and postnatal prostatic growth and development, for proper cell lineage specification within the prostate, as well as for adult prostate maintenance and regeneration following castration and hormone replacement. Evidence for Notch as a regulator of prostate cancer development, progression, and metastasis has also emerged. This review summarizes our current understanding of the role of Notch pathway elements, including members of the Jagged, Delta-like, hairy/enhancer-of-split, and hairy/enhancer-of-split related with YRPW motif families, in prostate development and tumorigenesis. Data supporting Notch pathway elements as oncogenes and tumor suppressors in prostate tumors, as well as data implicating Notch receptors and ligands as potential markers of normal prostate stem/progenitor cells and prostate cancer stem/initiating cells, are also presented.     

MCM7 silencing promotes cutaneous melanoma cell autophagy and apoptosis by inactivating the AKT1/mTOR signaling pathway

Cutaneous melanoma (CM) has become a major public health concern. Studies illustrate that minichromosome maintenance protein 7 (MCM7) participate in various diseases including skin disease. Our study aimed to study the effects of MCM7 silencing on CM cell autophagy and apoptosis by modulating the AKT threonine kinase 1 (AKT1)/mechanistic target of rapamycin kinase (mTOR) signaling pathway. Initially, microarray analysis was used to screen the CM-related gene expression data as well as differentially expressed genes. Subsequently, MCM7 expression vector and lentivirus RNA used for MCM7 silencing (LV-shRNA-MCM7) were constructed, and these vectors, dimethyl sulfoxide (DMSO) and AKT activator SC79 were then introduced into CM cell line SK-MEL-2 to validate the role of MCM7 in cell autophagy, viability, apoptosis, cell cycle, migration, and invasion. To further investigate the regulatory mechanisms of MCM7 in CM progress, the expression of MCM7, AKT1, mTOR, cyclin D1, as well as autophagy and apoptosis relative factors, such as LC3B, SOD2, DJ-1, p62, Bcl-2, Bax, and caspase-3 in melanoma cells was determined. MCM7 might mediate the AKT1/mTOR signaling pathway to influence the progress of melanoma. MCM7 silencing contributed to the increased expression of Bax, capase-3, and autophagy-related genes (LC3B, SOD2, and DJ-1), but decreased the expression of Bcl-2, which suggested that MCM7 silencing promoted autophagy and cell apoptosis. At the same time, MCM7 silencing also attenuated cell viability, invasion, and migration, and reduced the cyclin D1 expression and protein levels of p-AKT1 and p-mTOR. Taken together, MCM7 silencing inhibited CM via inactivation of the AKT1/mTOR signaling pathway.     

Silver nanoparticles regulate autophagy through lysosome injury and cell hypoxia in prostate cancer cells

With the rapid development of nanotechnology, nanomaterials are now being used for cancer treatment. Although studies on the application of silver nanoparticles in cancer treatment are burgeoning, few studies have investigated the toxicology mechanisms of autophagy in cancer cells under exposure to sublethal silver nanoparticles. Here, we clarified the distinct mechanisms of silver nanoparticles for the regulation of autophagy in prostate cancer PC‐3 cells under sublethal exposure. Silver nanoparticle treatment caused lysosome injury, including the decline of lysosomal membrane integrity, decrease of lysosomal quantity, and attenuation of lysosomal protease activity, which resulted in blockage of autophagic flux. In addition, sublethal silver nanoparticle exposure activated AMP‐activated protein kinase/mammalian target of rapamycin‐dependent signaling pathway to modulate autophagy, which resulted from silver nanoparticles‐induced cell hypoxia and energy deficiency. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in PC‐3 cells under sublethal dose exposure. This study will provide an experimental basis for the cancer therapy of nanomaterials.     

Zingerone suppresses cell proliferation via inducing cellular apoptosis and inhibition of the PI3K/AKT/mTOR signaling pathway in human prostate cancer PC‐3 cells

Prostate cancer (PCa) is both the foremost and second cause of cancer death in the male population. Patients with hormone‐dependent PCa are initially sensitive to androgen‐deprivation therapy, later the cancer progress to a hormone‐independent state and fails to respond and progress to the metastatic stage, where the cells gain the ability to escape cell death and develop resistance to current therapies, thereby leading to migration, invasion, and metastasis of cancer. Many clinical trials using nutraceuticals on cancer using human subjects have also been extensively studied, these studies confirm the efficacy of drugs tested in in vitro and in vivo preclinical models. Among various dietary phytochemicals, ginger is commonly used in the diet and possesses many active principles that act against cancer. Among various active principles, zingerone is a key active phenolic compound present in Zingiber officinale (Ginger), it has potent antioxidant property and it acts against carcinogens. The present study evaluated the efficacy of zingerone at different doses on the PCa cell line regarding apoptosis, upstream signing molecules such as Akt/mTOR, and migration metastasis. A cell viability assay using MTT was performed to estimate the percentage of viability of zingerone‐treated PC‐3 cells. The mitochondrial membrane potential, intracellular reactive oxygen species, and apoptosis induction in the zingerone‐treated PC‐3 cells were studied by using different fluorescence staining techniques. The expression patterns of PI3K, AKT, p‐AKT, mTOR, and p‐mTOR were investigated through the Western blot analysis assay. Zingerone induces apoptosis and alters Akt/mTOR molecules; it also inhibits cell adhesion and migration of PCa cells. From the present study, it is concluded that zingerone effectively induces apoptosis and inhibits cancer signaling, thereby acting as a potent drug against PCa.     

Clusterin enhances AKT2-mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit

Clusterin (CLU) is a chaperone-like protein with multiple functions. sCLU is frequently upregulated in prostate tumor cells after chemo- or radiotherapy and after surgical or pharmacological castration. Moreover, CLU has been documented to modulate the cellular homolog of murine thymoma virus akt8 oncogene (AKT) activity. Here, we investigated how CLU overexpression influences phosphatidylinositol 3′-kinase (PI3K)/AKT signaling in human normal and cancer epithelial prostate cells. Human prostate cells stably transfected with CLU were broadly profiled by reverse phase protein array (RPPA), with particular emphasis on the PI3K/AKT pathway. The effect of CLU overexpression on normal and cancer cell motility was also tested. Our results clearly indicate that CLU overexpression enhances phosphorylation of AKT restricted to isoform 2. Mechanistically, this can be explained by the finding that the phosphatase PH domain leucine-rich repeat-containing protein phosphatase 1 (PHLPP1), known to dephosphorylate AKT2 at S474, is markedly downregulated by CLU, whereas miR-190, a negative regulator of PHLPP1, is upregulated. Moreover, we found that phosphatase and tensin homolog (PTEN) was heavily phosphorylated at the inhibitory site S380, contributing to the hyperactivation of AKT signaling. By keeping AKT2 phosphorylation high, CLU dramatically enhances the migratory behavior of prostate epithelial cell lines with different migratory and invasive phenotypes, namely prostate normal epithelial 1A (PNT1A) and prostatic carcinoma 3 (PC3) cells. Altogether, our results unravel for the first time a circuit by which CLU can switch a low migration phenotype toward a high migration phenotype, through miR-190-dependent downmodulation of PHLPP1 expression and, in turn, stabilization of AKT2 phosphorylation.     

Ivermectin induces PAK1-mediated cytostatic autophagy in breast cancer

Ivermectin is a broad-spectrum antiparasitic drug that has recently been demonstrated to exhibit potent anticancer activity against colon cancer, ovarian cancer, melanoma and leukemia. However, the molecular mechanism underlying this anticancer effect remains poorly understood. We recently found that ivermectin markedly inhibits the growth of breast cancer cells by stimulating cytostatic macroautophagy/autophagy in vitro and in vivo. Ivermectin inhibits the AKT-MTOR signaling pathway by promoting ubiquitination-mediated degradation of PAK1 (p21 [RAC1] activated kinase 1), leading to increased autophagic flux. Together, our work unravels the molecular mechanism underpinning ivermectin-induced cytostatic autophagy in breast cancer, and characterizes ivermectin as a potential therapeutic option for breast cancer treatment.     

Dual roles of E-cadherin in prostate cancer invasion

The role(s) of E-cadherin in tumor progression, invasion, and metastasis remains somewhat enigmatic. In order to investigate various aspects of E-cadherin biological activity, particularly in prostate cancer progression, our laboratory cloned unique subpopulations of the heterogeneous DU145 human prostatic carcinoma cell line and characterized their distinct biological functions. The data revealed that the highly invasive, fibroblastic-like subpopulation of DU145 cells (designated DU145-F) expressed less than 0.1-fold of E-cadherin protein when compared to the parental DU145 or the poorly invasive DU145 cells (designated DU145-E). Experimental disruption of E-cadherin function stimulated migration and invasion of DU145-E and other E-cadherin-positive prostate cancer cell lines, but did not affect the fibroblastic-like DU145-F subpopulation. Within the medium of parental DU145 cells, the presence of an 80 kDa E-cadherin fragment was detected. Subsequent functional analyses revealed the stimulatory effect of this fragment on the migratory and invasive capability of E-cadherin-positive cells. These results suggest that E-cadherin plays an important role in regulating the invasive potential of prostate cancer cells through an unique paracrine mechanism.     

Targeting of distinct signaling cascades and cancer-associated fibroblasts define the efficacy of Sorafenib against prostate cancer cells

Sorafenib, a multi-tyrosine kinase inhibitor, kills more effectively the non-metastatic prostate cancer cell line 22Rv1 than the highly metastatic prostate cancer cell line PC3. In 22Rv1 cells, constitutively active STAT3 and ERK are targeted by sorafenib, contrasting with PC3 cells, in which these kinases are not active. Notably, overexpression of a constitutively active MEK construct in 22Rv1 cells stimulates the sustained phosphorylation of Bad and protects from sorafenib-induced cell death. In PC3 cells, Src and AKT are constitutively activated and targeted by sorafenib, leading to an increase in Bim protein levels. Overexpression of constitutively active AKT or knockdown of Bim protects PC3 cells from sorafenib-induced killing. In both PC3 and 22Rv1 cells, Mcl-1 depletion is required for the induction of cell death by sorafenib as transient overexpression of Mcl-1 is protective. Interestingly, co-culturing of primary cancer-associated fibroblasts (CAFs) with 22Rv1 or PC3 cells protected the cancer cells from sorafenib-induced cell death, and this protection was largely overcome by co-administration of the Bcl-2 antagonist, ABT737. In summary, the differential tyrosine kinase profile of prostate cancer cells defines the cytotoxic efficacy of sorafenib and this profile is modulated by CAFs to promote resistance. The combination of sorafenib with Bcl-2 antagonists, such as ABT737, may constitute a promising therapeutic strategy against prostate cancer.     

MET inhibition enhances PARP inhibitor efficacy in castration-resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways

Up to 30% of patients with metastatic castration-resistant prostate cancer (CRPC) patients carry altered DNA damage response genes, enabling the use of poly adenosine diphosphate–ribose polymerase (PARP) inhibitors in advanced CRPC. The proto-oncogene mesenchymal–epithelial transition (MET) is crucial in the migration, proliferation, and invasion of tumour cells. Aberrant expression of MET and its ligand hepatocyte growth factor is associated with drug resistance in cancer therapy. Here, we found that MET was highly expressed in human CRPC tissues and overexpressed in DU145 and PC3 cells in a drug concentration-dependent manner and is closely related to sensitivity to PARP inhibitors. Combining the PARP inhibitor olaparib with the MET inhibitor crizotinib synergistically inhibited CRPC cell growth both in vivo and in vitro. Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells. In conclusion, we demonstrated that MET inhibition enhances sensitivity of CRPC to PARP inhibitors by suppressing the ATM/ATR and PI3K/AKT pathways and provides a novel, targeted therapy regimen for CRPC.     

Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells

Background: Oridonin (ORI) could inhibit the proliferation and induce apoptosis in various cancer cell lines. However, the mechanism is not fully understood.Methods: Human prostate cancer (HPC) cells were cultured in vitro and cell viability was detected by the CCK-8 assay. The ultrastructure changes were observed under transmission electron microscope (TEM). Chemical staining with acridine orange (AO), MDC or DAPI was used to detect acidic vesicular organelles (AVOs) and alternation of DNA. Expression of LC3 and P21 was detected by Western Blot. Apoptotic rates and cell cycle arrest were detected by FACS.Results: Our study demonstrated that after ORI treatment, the proliferations of human prostate cancer (HPC) cell lines PC-3 and LNCaP were inhibited in a concentration and time-dependent manner. ORI induced cell cycle arrest at the G2/M phase. A large number of autophagosomes with double-membrane structure and acidic vesicular organelles (AVOs) were detected in the cytoplasm of HPC cells treated with ORI for 24 hours. ORI resulted in the conversion of LC3-I to LC3-II and recruitment of LC3-II to the autophagosomal membranes. Autophagy inhibitor 3-methyladenine (3-MA) reduced AVOs formation and inhibited LC3-I to LC3-II conversion. At 48 h, DNA fragmentation, chromatin condensation and disappearance of surface microvilli were detected in ORI-treated cells. ORI induced a significant increase in the number of apoptotic cells (PC-3: 5.4% to 27.0%, LNCaP: 5.3% to 31.0%). Promoting autophagy by nutrient starvation increased cell viability, while inhibition of autophagy by 3-MA promoted cell death. The expression of P21 was increased by ORI, which could be completely reversed by the inhibition of autophagy.Conclusions: Our findings indicated that autophagy occurred before the onset of apoptosis and protected cancer cells in ORI-treated HPC cells. P21 was involved in ORI-induced autophagy and apoptosis. Our results provide an experimental basis for understand the anti-tumor mechanism of ORI as treatment for prostate cancer.     

Inhibition of autophagy enhances apoptosis induced by the PI3K/AKT/mTor inhibitor NVP‐BEZ235 in renal cell carcinoma cells

The PI3K/AKT/mTOR pathway plays a key role in the development of the hypervascular tumor renal cell carcinoma (RCC). NVP‐BEZ235 (NVP), a novel dual PI3K/mTOR inhibitor, showed great antitumor benefit and provided a treatment strategy in RCC. In this study, we test the effect of NVP on survival rate, apoptosis and autophagy in the RCC cell line, 786‐0. We also explore the hypothesis that NVP, in combination with autophagy inhibitors, leads to apoptosis enhancement in 786‐0 cells. The results showed that the PI3K/AKT/mTOR pathway proteins p‐AKT and p‐P70S6K were highly expressed in RCC tissue. We also showed that NVP inhibited cell growth and induced apoptosis and autophagy in RCC cells. The combination treatment of NVP with autophagy inhibitors enhanced the effect of NVP on suppressing 786‐0 growth and induction of apoptosis. This study proposes a novel treatment paradigm where combining PI3K/AKT/mTOR pathway inhibitors and autophagy inhibitors lead to enhanced RCC cell apoptosis. Copyright © 2012 John Wiley & Sons, Ltd.     

自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效的相关性分析

对晚期非小细胞肺癌患者采用含铂化疗是肺癌临床治疗中非常重要的方法,然而不同患者对含铂化疗的敏感性却存在着明显的个体差异,这提示发现潜在的分子标志物对预测临床中含铂化疗疗效具有关键作用。本研究旨在探索自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效之间的相关性,以期寻找可能影响含铂化疗药物敏感性的分子标记。本研究纳入了1004例接受含铂化疗的晚期非小细胞肺癌患者,分析了自噬通路中13个基因上的99个SNP位点与含铂化疗临床获益、无疾病进展时间及总生存时间之间的相关性。研究发现,位于ULK1基因的位点rs7953348(G>A) (P=0.017, OR:0.67, 95%CI:0.49~0.93)和rs12303764(A>C) (P=0.009, OR:0.63, 95%CI:0.45-0.89)及位于ATG14基因上的位点rs17742719(C>A) (P=0.002, OR:1.83, 95%CI:1.26~2.66)、rs8003279(A>G) (P=0.006, OR:1.65, 95%CI:1.16~2.35)和rs1009647(G>A) (P=0.002, OR:1.70, 95%CI:1.22~2.37)与临床获益存在显著关联,位于DRAM基因上的位点rs7955890(G>A) (P=0.004, HR:0.63; 95%CI:0.46~0.86)和rs17032060(G>A) (P=0.006, HR:0.65, 95%CI:0.48~0.88)及位于ATG3基因上的位点rs13082005(G>A) (P=0.012, HR:1.27,95%CI:1.05~1.53)与含铂化疗的无疾病进展时间显著相关,位于ULK1基因的位点rs7953348(G>A) (P=0.011, HR:0.74, 95%CI:0.58~0.93)和位于ATG10基因上的位点rs1864183(G>A) (P=0.016, HR:0.42, 95%CI:0.21~0.85)对含铂化疗的总生存时间有着显著影响。研究结果提示自噬通路在含铂化疗敏感性中发挥着重要作用,自噬通路基因多态性可能是预测含铂化疗疗效的潜在分子标志物,这可能为临床上肺癌的个体化医疗提供一定的理论基础。     

High-mobility group box 2 promoted proliferation of cervical cancer cells by activating AKT signaling pathway

Cervical cancer is one of the leading killers for female worldwide. Nevertheless, the less knowledge of molecular mechanism for cervical cancer limited the improvement of treatment effects. High-mobility group box 2 (HMGB2) belongs to the HMGB family, which could play diverse roles in cell proliferation. This work mainly aimed to study the functions of HMGB2 on cervical cancer cells proliferation. HMGB2 was highly expressed in cervical cancer tissue. The results of real-time polymerase chain reaction and Western blot analysis showed that HMGB2 was expressed in all the five cervical cancer cells (HeLa, CaSki, SiHa, C-33A, and C4-1 cells). In addition, HMGB2 overexpression obviously improved cell viability and promoted cell cycle progression, which suggested that HMGB2 could promote proliferation of cervical cancer cells. Moreover, HMGB2 overexpression increased the level of p-AKT and reduced the levels of p21 and p27. However, HMGB2 downregulation had contrary influences on cell proliferation, cell cycle distribution and the levels of p-AKT, p21, and p27. Notably, LY294002, as an inhibitor of AKT signaling pathway, could significantly weaken the effects of HMGB2 overexpression, which indicated that HMGB2 might promote cell proliferation by activating AKT signaling pathway. Therefore, HMGB2 was hopeful to be a candidate as a new biomarker and therapy target for cervical cancer.