胃癌中显著下调的miR-433的作用靶点研究

目的为了筛选胃癌中miRNAs的表达标记,验证胃癌相关miRNAs的作用靶点,建立一种新的诊断和治疗胃癌的方法。方法运用基因芯片技术检测3个正常胃组织标本,24个胃癌组织标本,胃癌细胞SGC7901和正常胃黏膜细胞GES-1中328个miRNAs的表达情况。用以上方法检测出在胃癌组织和SGC7901中,miR-433的表达水平显著下调。为了确保结果的准确性,采用实时荧光定量PCR对其进行验证。并用基因克隆和Western印迹方法分析miR-433的作用靶点。结果共有26个miRNAs在胃癌标本（包括24个胃癌组织和SGC7901）中异常表达。其中19个miRNAs下调,7个miRNAs上调。实时荧光定量PCR检测出miR-433在胃癌标本中的表达水平显著下调,该结果和基因芯片检测结果一致。另外,在本实验中发现miR-433与Grb2（growth factor receptor—bound protein 2）的表达呈负相关。结论胃癌相关miRNAs已进行了初步筛选。其中,miR-433可能是胃癌中的标记性miRNAs之一,Grb2是其作用靶点。这为建立新的以miRNAs为基础的诊断和治疗胃癌的方法提供了相关信息。     

MicroRNA let-7f inhibits tumor invasion and metastasis by targeting MYH9 in human gastric cancer

Background

MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers.

Methodology/Principal

Real-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3′UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels.

Conclusions/Significance

Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis.     

Mad2beta, an alternative variant of Mad2 reducing mitotic arrest and apoptosis induced by adriamycin in gastric cancer cells

Mad2beta is an alternative splicing variant of spindle checkpoint gene mad2, which was previously found by us and was related to the drug resistance in gastric cancer cells. In this paper, we explored the molecular mechanisms that Mad2beta variant promoted the formation of multidrug resistance in gastric cancer cells. We found that Mad2beta variant was detected only in the two human drug resistant gastric cancer cell sublines SGC7901/VCR and SGC7901/ADR, and it did not appear in its parental cell line SGC7901 and other detected gastric cancer cell lines. Expressions of Mad2 mRNA and protein in SGC7901 cells transfected with Mad2beta, SGC7901/VCR and SGC7901/ADR were significantly lower than that in SGC7901 cells. Moreover, SGC7901 cells overexpressing Mad2beta variant became more resistant to adriamycin, vincristine and mitomycin by abrogating mitotic arrest and apoptosis. This suggests that expression of Mad2beta variant decreases the relative expression of efficient MAD2, which may help gastric cancer cells to develop the phenotype of multidrug resistance.     

长链非编码RNA UCA1在胃癌多药耐药中的作用研究

目的:研究胃癌耐药细胞及其亲本细胞中长链非编码RNA UCA1的表达差异,探讨UCA1在胃癌多药耐药中的作用。方法:通过实时荧光定量PCR(q RT-PCR)检测胃癌耐药细胞SGC7901/ADR、SGC7901/VCR及其亲本细胞SGC7901中UCA1的表达差异;通过si RNA转染降低SGC7901/ADR中UCA1表达,MTT法检测细胞半数抑制浓度(IC50)的变化,流式细胞仪检测细胞凋亡变化。结果:QRT-PCR结果显示,UCA1在SGC7901/ADR和SGC7901/VCR胃癌耐药细胞表达显著高于SGC7901胃癌亲本细胞;MTT实验表明,干扰UCA1的SGC7901/ADR相对于阴性对照(NC)组的IC50显著降低;凋亡检测结果显示,在相同剂量化疗药物作用下,干扰UCA1后SGC7901/ADR凋亡率显著高于NC组;Western blot证实,干扰UCA1表达可显著降低BCL-2蛋白表达。结论:长链非编码RNA UCA1在胃癌耐药细胞表达显著升高,干扰UCA1表达可明显逆转胃癌耐药,UCA1可作为治疗胃癌耐药的重要分子靶标。     

Depression of MAD2 inhibits apoptosis of gastric cancer cells by upregulating Bcl-2 and interfering mitochondrion pathway

Mitotic arrest deficient 2 (MAD2) is an essential component of the mitotic spindle checkpoint pathway. It was previously shown to be associated with drug resistance of tumor cells. To further explore the roles of MAD2 in responses of gastric cancer cells to chemotherapy drugs, we constructed the siRNA vectors of MAD2 and transfected them into gastric cancer SGC7901 cells to inhibit expression of MAD2. MTT assay showed that the downregulation of MAD2 increased the resistance of SGC7901 cells to spindle inhibitors and DNA damaging agents. The apoptosis rates of gastric cancer cells transfected with MAD2-siRNA were 10.7% and 10%, respectively, after treated by 1.0microg/ml VCR and cisplatin. In contrast, the apoptosis rates of SGC7901 and SGC7901/psilencer3.1 induced by VCR were 43.2%, 38.7%; and that induced by cispaltin were 34.1%, 31.4%. The ratio of Bcl-2 to Bax was much higher in the MAD2-siRNA transfectants compared with the SGC7901/psilencer. In SGC7901/psilencer, cytochrome c and cleaved caspase 3 protein levels increased along with the exposure time increased. However, these protein levels of SGC7901/MAD2-siRNA had no changes during the drug treatment. These results indicate that down regulation of MAD2 could promote the drug resistance of gastric cancer cells and inhibit anticancer drugs induced-apoptosis by upregulating Bcl-2 and interfering the mitochondrion apoptosis pathway.     

MiR-935通过其靶基因Notch1调控胃癌SGC7901细胞的发生发展

目的:探究Mi R-935调控胃癌SGC7901细胞的增殖和浸润与Notch1基因表达的关系。方法:分别检测40例正常人胃粘膜组织与40例胃印戒细胞癌的Notch1表达情况,并分析胃印戒细胞癌组织中Notch1表达与患者年龄、性别、组织进展程度、TNM分期、有无淋巴结转移的关系;采用Mi R-935转染体外培养的SGC7901细胞系,检测Notch1的表达情况,其后采用Mi R-935抑制剂处理,通过Transwell实验检测胃癌细胞的侵袭能力,细胞划痕实验检测胃癌细胞迁移能力。结果:正常人胃粘膜组织中Notch1表达呈阴性,而胃印戒细胞癌组织中Notch1表达呈阳性;Notch1的表达与胃印戒细胞癌的TNM分期、有无淋巴结转移存在着显著的相关性;转染Mi R-935的SGC7901细胞Notch1表达明显上调,采用Mi R-935抑制剂处理后,Notch1的表达显著下降。结论:Mi R-935可能通过调控Notch1的表达调控胃癌的扩增和浸润。     

CXXC finger protein 4 inhibits the CDK18‐ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway

Gastric cancer, is the fourth most common tumour type yet, ranks second in terms of the prevalence of cancer‐related deaths worldwide. CXXC finger protein 4 (CXXC4) has been considered as a novel cancer suppressive factor, including gastric cancer. This study attempted to investigate the possible function of CXXC4 in gastric cancer and the underlying mechanism. The binding of the ETS domain‐containing protein‐1 (ELK1) to the long non‐coding RNA MIR100HG promoter region was identified. Then, their expression patterns in gastric cancer tissues and cells (SGC7901) were detected. A CCK‐8 assay was used to detect SGC7901 cell proliferation. Subsequently, SGC7901 cells were co‐cultured with CD3+ T cells, followed by measurement of CD3+ T cell proliferation, magnitude of IFN‐γ+ T cell population and IFN‐γ secretion. A nude mouse model was subsequently developed for in vivo validation of the in vitro results. Low CXXC4 expression was found in SGC7901 cells. Nuclear entry of ELK1 can be inhibited by suppression of the extent of ELK1 phosphorylation. Furthermore, ELK1 is able to bind the MIR100HG promoter. Overexpression of CXXC4 resulted in weakened binding of ELK1 to the MIR100HG promoter, leading to a reduced proliferative potential of SGC7901 cells, and an increase in IFN‐γ secretion from CD3+ T cells. Moreover, in vivo experiments revealed that CXXC4 inhibited immune escape of gastric cancer cells through the ERK1/2 axis. Inhibition of the CXXC4/ELK1/MIR100HG pathway suppressed the immune escape of gastric cancer cells, highlighting a possible therapeutic target for the treatment of gastric cancer.     

胃癌多药耐药相关microRNA的筛选和鉴定

目的:研究胃癌多药耐药相关microRNA并对其进行鉴定、靶基因预测和预测靶基因的生物信息学分析。方法:运用microRNA芯片对胃癌多药耐药细胞SGC7901/ADR和其亲本细胞SGC7901进行microRNA表达谱分析;采用实时定量PCR的方法对差异表达的miRNA进行验证;再运用生物信息学方法对差异表达的miRNA进行靶基因预测;再对预测的靶基因进行GO和KEGG通路分析。结果:与SGC7901相比SGC7901/ADR表达上调超过2倍的miRNA有6个,表达下调超过2倍的有11个。实时定量PCR对共同差异表达的microRNA进行验证显示与芯片结果的一致性。对这17个差异表达的miRNA进行靶基因预测,再对预测得到的靶基因进行GO和KEGG通路分析显示预测的靶基因参与了肿瘤相关通路、MAPK通路、Focal Adhesion通路等。结论:我们初步筛选得到了胃癌多药耐药相关miRNA并对其进行了生物信息学分析,为进一步地探索miRNA在胃癌多药耐药中的作用及其分子机制奠定了基础。     

Cycloxygenase-2 is Essential for the Survival and Proliferation of Gastric Cancer Cells

Cycloxygenase-2 catalyzes the synthesis of prostaglandins from arachidonic acid and this enzyme has been implicated in the metastasis of gastric cancer. In order to examine the significance of cycloxygenase-2 (Cox-2) in the survival and proliferation of gastric cancer cells, we have stably overexpressed an antisense Cox-2 in two gastric cancer cell lines, SGC7901 and AGS, in order to reduce the expression of this protein. The sense and antisense Cox-2 expression vectors were created by cloning COX-2 cDNA, in pIRES2-EGFP plasmid. Cox-2 gene expression was monitored by RT-PCR and Western blotting and the results indicated that cells with antisense Cox-2 construct had significantly reduced Cox-2 expression in comparison to the cells that received sense-Cox-2 plasmid. Reduction of Cox-2 expression in SGC7901 and AGS gastric cancer cells led to markedly decreased proliferation. The metastatic capability of the two cell lines, as assessed by in vitro colony formation assay, is also significantly compromised by lowered Cox-2 expression. Thus, this study demonstrates that Cox-2 activity is necessary for the proliferation and metastasis of gastric cancer cells.     

Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901

We aimed to study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation, apoptosis, and autophagy in gastric cancer cell line SGC7901. In this study, we showed that LY294002 inhibited the viability of gastric cancer SGC7901 cells. We also showed that LY294002 increased the expression of microtubule-associated protein 1 light chain 3 (LC3), and increased monodansylcadaverine (MDC)-labeled vesicles. LY294002 activated autophagy by activating p53 and caspase-3, and induced apoptosis by up-regulatingp53 and p53-up-regulated modulator of apoptosis ( PUMA ). Therefore, LY294002 might induce cytotoxicity in SGC7901 cells through activation of p53 and the downstream point PUMA . These findings suggest that inhibition of the class I PI3K signaling pathway is a potential strategy for managing gastric cancers.     

Sunitinib Reverse Multidrug Resistance in Gastric Cancer Cells by Modulating Stat3 and Inhibiting P-gp Function

Sunitinib, a small-molecule multi-targeted tyrosine kinase inhibitor, has been applied in phase II clinical trial as second-line treatment for advanced gastric cancer. In this study, we determined the effect of Sunitinib on the multidrug resistance in gastric cancer cells selected by vincristine. Our results showed that Sunitinib significantly enhanced the cytotoxicity of adriamycin, vincristine, etoposide, 5-Fluorouracil, and cisplatin in multidrug-resistant gastric cancer cells (SGC7901/VCR). Sunitinib significantly increased the intracellular accumulation and retention of rhodamine 123 in the SGC7901/VCR cells. However, Sunitinib, at a concentration that reverses MDR, had no significant effect on P-gp protein or mRNA expression levels. In addition, the present study revealed that Sunitinib inhibited Stat3 and down-regulated Bcl-2 in SGC7901/VCR cells, which might also contribute to the reversal of MDR. In conclusion, Sunitinib reverses multidrug resistance in gastric cancer cells by inhibiting P-gp transporter function and modulating Stat3 and Bcl-2. Further study with Sunitinib may be helpful for developing combination therapeutic strategy or circumventing gastric cancer MDR to other conventional anti-cancer drugs.     

应用蛋白质组学技术筛选胃癌耐药相关蛋白质

胃癌多药耐药性是临床胃癌化疗失败最主要的原因之一,但其分子机制仍然不太清楚.为了寻找新的胃癌耐药相关的蛋白质,揭示胃癌多药耐药的分子机制,以胃癌细胞SGC7901和长春新碱诱导的耐药胃癌细胞SGC7901/VCR为研究对象,应用二维凝胶电泳(two-dimensionalelectrophoresis,2-DE)技术分离两种细胞的总蛋白质,图像分析识别差异表达的蛋白质点,基质辅助激光解吸电离飞行时间质谱(matrix-assistedlaserdesorption/ionizationtimeofflightmassspectrometry,MALDI-TOF-MS)及电喷雾电离串联质谱(electrosprayionizationtandemmassspectrometry,ESI-Q-TOF)对差异表达的蛋白质点进行鉴定,蛋白质印迹和实时RT-PCR验证部分差异蛋白质在两株细胞中的表达水平,反义核酸转染技术分析HSP27(heatshockprotein27,HSP27)高表达与SGC7901/VCR耐药的相关性.得到了分辨率较高、重复性较好的两株细胞系的二维凝胶电泳图谱,质谱分析共鉴定了24个差异蛋白质点,蛋白质印迹和实时RT-PCR验证了部分差异蛋白的表达水平,反义寡核苷酸抑制HSP27表达能增加SGC7901/VCR对长春新碱的敏感性.研究结果不仅提示这些差异蛋白质如HSP27,Sorcin等可能与胃癌的多药耐药相关,而且为揭示胃癌细胞的多药耐药性产生机制提供了线索.     

Proteome analysis of multidrug resistance in vincristine-resistant human gastric cancer cell line SGC7901/VCR

In order to elucidate the mechanisms of multidrug resistance (MDR) of vincristine-resistant human gastric carcinoma cell line SGC7901/VCR, 2-DE was used to separate the total proteins of SGC7901/VCR and its parental cell line SGC7901. PDQuest software was applied to analyze 2-DE images, and the differential protein spots were identified by both MALDI-TOF-MS and ESI-Q-TOF-MS. Then the differential expressional levels of partially identified proteins were determined by Western blot analysis and real-time RT-PCR. Furthermore, the association of heat shock protein (HSP27), one of the highly expressed proteins in sgc7901/vcr, with MDR was analyzed using antisense inhibition of HSP27. In this study, the well-resolved, reproducible 2-DE patterns of SGC7901/VCR and SGC7901 were established, and yielded about 1100 protein-spots each. All the 24 differential proteins between the two cell lines were identified, and the differential expression levels of the partial proteins were confirmed. The suppression of HSP27 expression by HSP27 antisense oligonucleotides could enhance vincristine chemosensitivity in sgc7901/vcr and induce the cells to exhibit apoptotic morphological features after vincristine treatment. The differentially expressed proteins could be divided into six groups based on their functions: calcium-binding proteins, chaperones, proteins involved in drug detoxification or repair of DNA damage, metabolic enzymes, proteins related to cellular structure, and proteins relative to signal transduction, some of which may contribute to MDR of human gastric carcinoma cell line SGC7901/VCR. These data will be valuable for further study of the mechanisms of MDR in human gastric cancer.     

Activation of LXRβ inhibits proliferation,promotes apoptosis,and increases chemosensitivity of gastric cancer cells by upregulating the expression of ATF4

Recently, great advances have been achieved in both surgery and chemotherapy for the treatment of gastric cancer, but there is still poor prognosis for this disease. The aim of this study is to investigate the role of liver X receptor β (LXRβ) in chemosensitivity of gastric cancer SGC7901 cells. From 171 patients with gastric cancer, the gastric cancer and paracancerous tissues were selected to measure the expression of LXRβ and ATF4. Gastric cancer cell lines were cultured and screened to figure out the proliferation and apoptosis of gastric cancer SGC7901 cells with the treatment of LXRβ agonist (GW3965), ATF4 short hairpin RNA (shRNA), and chemotherapy drug paclitaxel. The expression of apoptosis-related gene cleaved caspase-3 was detected by Western blot analysis. First, we found that the expressions of LXRβ and ATF4 in gastric cancer tissues and cells were significantly lower than those in their paracancerous tissues and gastric mucosal epithelial cells. In addition, activation of LXRβ and paclitaxel treatment suppressed proliferation of SGC7901 cells, and the expression of ATF4 was upregulated in a concentration-dependent manner. Furthermore, shRNA significantly inhibited the expression of ATF4 and blocked the chemosensitivity of SGC7901 cells to LXRβ activation. Our study demonstrates that the expression of LXRβ was low in gastric cancer. In addition, activation of LXRβ may inhibit the proliferation of gastric cancer cells, promote apoptosis, and increase chemosensitivity by upregulating the expression of ATF4.     

Trefoil factor 3 peptide regulates migration via a Twist-dependent pathway in gastric cell

Trefoil factor 3 (TFF3) is a member of the TFF-domain peptide family and essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. However, the role of TFF3 and its downstream regulating mechanisms in cancer cell migration remain unclear. We previously reported that TFF3 prolonged the up-regulation of Twist protein to modulate IL-8 secretion in intestinal epithelial cells. In this study, we investigated the role of Twist protein in TFF3-induced migration of SGC7901 cells. While Twist was activated by TFF3, siRNA-mediated knockdown of Twist abolished TFF3-induced cell migration. Furthermore, the migration related marker CK-8 as well as ZO-1 and MMP-9 was also regulated by TFF3 via a Twist-dependent mechanism. Our study suggests that Twist, as an important potential downstream effector, plays a key role in TFF3-modulated metastasis in gastric cancer and can be a promising therapeutic target against intestinal-type gastric cancer.     

Reversal of multidrug resistance of vincristine-resistant gastric adenocarcinoma cells through up-regulation of DARPP-32

Here we investigated the roles of DARPP-32 in multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. We constructed the eukaryotic expression vector of DARPP-32 and transfected it into human vincristine-resistant gastric adenocarcinoma cell line SGC7901/VCR. Up-regulation of DARPP-32 could significantly enhance the sensitivity of SGC7901/VCR cells towards vincristine, adriamycin, 5-fluorouracil and cisplatin, and could decrease the capacity of cells to efflux adriamycin. What's more, the results of subrenal capsule assay confirmed that DARPP-32 might play a certain role in MDR of gastric cancer. DARPP-32 could significantly down-regulate the expression of P-gp and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein (MRP) or the glutathione S-transferase (GST). DARPP-32 could also significantly decrease the anti-apoptotic activity of SGC7901/VCR cells. Further study of the biological functions of DARPP-32 might be helpful for understanding the mechanisms of MDR in gastric cancer.     

罗格列酮抑制人胃腺癌SGC7901增殖机制的研究

目的：探讨在体外不同浓度的过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮（ROZ）对人胃癌细胞系SGC7901的生长及细胞周期的影响。方法：采用MTT法比色实验、集落形成实验、电子显微镜,透射电镜,流式细胞仪分别观察不同浓度罗格列酮0.08μmol/L,0.4μmol/L,2μmol/L,10μmol/L,50μmol/L,作用于SGC7901细胞,对细胞增殖,细胞形态和细胞周期的影响。结果：ROZ可抑制SGC7901细胞的生长以及SGC7901细胞集落的形成,并呈现剂量依赖性,其半数抑制浓度（IC50）约为50μmol/L。透射电镜低倍镜以及高倍下可见凋亡细胞。流式细胞仪结果显示,ROZ可抑制SGC7901细胞,引起G0/G1期细胞大量增加,S期细胞减少,且细胞周期停滞于G1期。结论：ROZ具有抗肿瘤作用,能够抑制SGC7901细胞的增殖并诱导凋亡,这种作用与其诱导细胞周期G0/G1期的停滞和诱导凋亡作用有关。因此,ROZ有望成为胃癌治疗的辅助用药亦或治疗药,PPARγ有潜力成为肿瘤治疗的新靶点。     

内源性活性氧水平及锰型超氧化物歧化酶的表达与胃癌细胞分化、增殖相关

检测了不同分化的胃癌细胞株内MnSOD基因的表达及胞内活性氧限（ROS)的水平。同时通过基因转染观察上调或下调MnSOD基因表达对SGC790l胃癌细胞胞内ROS水平及增殖能力的影响。用电穿孔法将人反义和正义MnSOD cDNA真核表达载体pHβA—SOD(-)／pHβA—SOD（ )转入790l细胞,用含G418的RPMIl640培养基筛选稳定表达克隆。然后用RT-PCR鉴定MnDSOD基因的表达。同时用RT-PCR方法检测正常胃粘膜组织及MKN-28、SGC790l、BGC823、HGC-27四株高、中、低、未分化胃癌细胞株内的MnSoD的mRNA表达。利用DCFH-DA荧光染色方法检测不同分化胃癌细胞株及790l转染细胞株内的ROS水平。四唑蓝比色法(MTT)绘制MKN-28、SGC790l、BGC823、HGC-27四株不同分化胃癌细胞及正义、反义、空载MnSOD转染790l细胞的生长曲线。发现不同分化胃癌细胞内的MnSOD普遍呈低表达且与分化程度平行,不同分化胃癌细胞株胞内ROS水平随着MnSOD表达的下调逐步上升,细胞增殖加快。较之MnSOD空载790l,正义、反义MnSOD转染的790l细胞中该基因的表达出现明显上调及下调,胞内ROS水平较对照细胞也相应有显著降低和升高。正义株增殖受抑,反义株增殖加快。表明胃癌细胞内MnSOD的表达与肿瘤的分化程度呈负相关。可通过改变胞内RoS水平改变MnSOD基因的表达,从而调节胃癌细胞的生长。     

腺病毒介导的EMC6基因通过下调FAK信号通路抑制胃癌细胞迁移

内质网膜蛋白复合物亚单位6（endoplasmic reticulum membrane protein complex subunit 6,EMC6）,也称穿膜蛋白93 (transmembrane protein 93, TMEM93)是我们首次报道的一个人类自噬相关分子。EMC6基因进化保守,表达广泛,在胃癌组织中表达下调或缺失。本研究利用构建的重组腺病毒5型EMC6（Ad5-EMC6）载体,感染胃癌细胞系BGC823和SGC7901,分析了其在肿瘤细胞的表达以及抗肿瘤活性。研究证明, Ad5-EMC6能够显著抑制胃癌细胞的克隆形成、细胞划痕修复、以及迁移和侵袭的能力。进一步的研究提示,Ad5-EMC6能够降低胃癌细胞局部黏着斑激酶（FAK）的Y576/577磷酸化水平,FAK下游的基质金属蛋白酶MMP2和MMP9的蛋白质水平也同时下调。在裸鼠的腹膜扩散模型中,Ad5-EMC6处理组的小鼠腹膜结节数量明显减少或缺失。这些研究数据提示, Ad5-EMC6介导的FAK信号灭活可能是其抑瘤活性的机制之一,其分子机制还需要进一步探讨。