激活蛋白1在双歧杆菌预防大肠癌生长中的作用

目的 :探索青春型双歧杆菌体内预防大肠癌的机制。方法 :首先建立大肠癌裸鼠移植瘤动物模型 ,将实验动物分为双歧杆菌预防组和肿瘤对照组 ,以激光共聚焦显微镜定量检测了大肠癌组织激活蛋白1(AP-1)中的 c-fos和 c-jun的含量。结果 :双歧杆菌预防组大肠癌移植瘤 c-jun和 c-fos的含量均明显低于肿瘤对照组 (P<0 .0 1)。结论 :青春型双歧杆菌可通过降低大肠癌移植瘤组织 AP-1中的 c-jun和 c-fos的表达这一途径来预防大肠癌的生长     

蛋白激酶C在双歧杆菌预防大肠癌生长中的作用

目的:从信号分子蛋白激酶C(PKC)这一角度探索青春型双歧杆菌预防大肠癌生长的途径.方法:建立大肠癌裸鼠移植瘤模型,用激光共聚焦显微镜测定大肠癌组织PKC α、βⅠ、βⅡ、γ、ε和ζ的含量.结果:荷瘤鼠经双歧杆菌预先处理后,其大肠癌组织PKC α和βⅡ的平均荧光强度明显低于肿瘤对照组(P＜0.01),而PKC βⅠ、γ、ε和ζ的平均荧光强度在两组间差异无显著性(P＞0.05).结论:青春型双歧杆菌体内可通过降低PKCα、βⅡ的活性来预防大肠癌的生长.     

血管形成在双歧杆菌预防大肠癌生长中的作用

目的 从血管形成角度探索青春型双歧杆菌预防大肠癌生长的途径。方法 建立大肠癌裸鼠移植瘤模型,以免疫组化法检测大肠癌组织血管内皮生长因子（VEGF）的蛋白表达水平及其微血管密度（MVD）。结果 双歧杆菌预防组大肠癌VEGF的阳性细胞密度及MVD的数量均明显低于肿瘤对照组（P〈0．01）。结论 青春型双歧杆菌能下调大肠癌VEGF的表达,进而抑制其血管形成,这可能是它预防大肠癌生长的途径之一。     

双歧杆菌预防大肠癌生长的信号转导机制

目的:从信号转导这一层次探索青春型双歧杆菌预防大肠癌生长的机制.方法:以大肠癌裸鼠移植瘤为动物模型,用膜结合法和免疫组化分别测定了大肠癌组织蛋白酪氨酸激酶(PTK)的含量以及NF-κB的表达.结果:双歧杆菌预防组大肠癌组织PTK的活性以及NF-κB的阳性细胞密度均明显低于肿瘤对照组(P＜0.01).结论:青春型双歧杆菌体内预防大肠癌生长的途径之一为降低其PTK的活性,同进抑制NF-κB的活化.     

双歧杆菌对实验性大肠癌凋亡促进基因表达的影响

目的：探讨青春型双歧杆菌体内诱导大肠癌裸鼠移植瘤细胞凋亡的具体途径。方法：以免疫组化法检测大肠癌移植瘤细胞凋亡促进基因bad和Caspase-3基因的蛋白表达率和阳性细胞密度。结果：双歧杆菌注射组大肠癌移植瘤细胞凋亡促进基因bad和Caspase-3基因的蛋白表达率以及阳性细胞密度均显著于肿瘤对照组。结论：双歧杆菌可通过促进bad和Caspase-3基因的表达,最终诱导大肠癌的凋亡。     

原位末端标记技术观察双歧杆菌诱导实验性大肠癌的凋亡

本文以大肠癌裸鼠移植瘤为动物模型,将实验分为双歧杆菌注射组以及肿瘤对照组,用原位末端标记法观察了移植瘤组织的凋亡细胞百分率。结果显示：双歧杆菌注射组大肠癌移植瘤的凋亡细胞百分率为２６４２８±１８６２,而对照组则为２０６２±８８０,两者比较具有显著的统计学意义（Ｐ＜０００１）。提示青春型双歧杆菌可诱导大肠癌组织的凋亡,这可能是其抑瘤机理的一个方面     

双歧杆菌的完整肽聚糖对实验性大肠癌凋亡控制基因表达的影响

为探讨双歧杆菌的完整肽聚糖的抑瘤途径及机制,本文以大肠癌裸鼠移植瘤为动物模型,采用免疫组化ＳＰ法检测了４０只裸鼠移植瘤ｂｃｌ－２及ｂａｘ基因的蛋白表达率及表达强度,结果显示肽聚糖注射组大肠癌移植瘤ｂｃｌ－２蛋白表达率及阳性细胞密度低于肿瘤对照组,ｂｃｘ基因的表达情况则相反。提示双歧杆菌的完整肽聚糖可使大肠癌裸鼠移植瘤的ｂｃｌ－２基因表达下调,ｂａｘ基因表达强,最终诱导肿瘤细胞凋亡,实现其抗瘤目的。     

双歧杆菌诱发实验性大肠癌凋亡的电镜观察

本文以大肠癌裸鼠移植瘤为动物模型,用透射电镜观察了青春型双歧杆菌对移植瘤超微结构的影响。结果表明：双歧杆菌经荷瘤鼠腹腔注射后能诱导多量大肠癌细胞凋亡,凋亡早期的细胞主要表现为核染色质浓缩边聚;中期为核膜破裂,胞核崩解,凋亡小体形成;晚期主要为邻近活细胞吞噬凋亡小体。提示双歧杆菌诱导大肠癌细胞程序化死亡可能是其抑瘤机制之一。     

丝裂素活化的蛋白激酶在双歧杆菌预防大肠癌中的作用

目的:从信号转导这一层次探索双歧杆菌预防大肠癌生长的机制.方法:以大肠癌裸鼠移植瘤为动物模型,预先用青春型双歧杆菌注射于裸鼠腹腔,然后以激光共聚焦显微镜检测大肠癌移植瘤组织丝裂素活化的蛋白激酶(MAPK)家系中的ERK1/2、JNK和p38的含量.结果:双歧杆菌预防组大肠癌组织ERK1/2的平均荧光强度明显低于肿瘤对照组(P＜0.01),而JNK和p38的平均荧光强度在两组间差异无显著性(P＞0.05).结论:青春型双歧杆菌通过抑制ERK1/2的活化来预防大肠癌的生长.     

双歧杆菌的完整肽聚糖对实验性大肠癌凋亡调控基因表达的影响

为探讨双歧杆菌的完整肽聚糖的抑瘤途径及机制,本文以大肠癌裸鼠移植瘤为动物模型,采用免疫组化ＳＰ法检测了４０只裸鼠移植瘤ｂｃｌ－２及ｂａｘ基因的蛋白表达率及表达强度。结果显示完整肽聚糖注射组大肠癌移植瘤ｂｃｌ－２蛋白表达率及阳性细胞密度均低于肿瘤对照组,ｂａｘ基因的表达情况则相反。提示双歧杆菌的完整肽聚糖可使大肠癌裸鼠移植瘤的ｂｃｌ－２基因表达下调,ｂａｘ基因表达增强,最终诱导肿瘤细胞凋亡,实现其抗瘤目的。     

Ursolic acid inhibits tumor angiogenesis and induces apoptosis through mitochondrial-dependent pathway in Ehrlich ascites carcinoma tumor

Ursolic acid (UA) is a pentacyclic triterpene naturally occurring in many plant foods. In the present study, we investigated anti-cancer activity of UA in vivo in Ehrlich ascites carcinoma (EAC) tumor. 15 × 10⁶ EAC cells were implanted intraperitoneally (i.p., ascitic tumor) and subcutaneous (s.c., solid tumor) in Swiss albino mice. Mice with established tumors received UA i.p. at 25, 50 and 100 mg/kg bw for 14 d in ascitic and 100 mg/kg bw in solid tumor for 30 d. On day 15, blood samples were collected for hematological assessment of hemoglobin (Hb%), RBCs, WBCs and PCV. Tumor volume, cell viability, angiogenic, anti-angiogenic, anti-inflammatory factors and antioxidant parameters were determined. Immunohistochemistry analysis for VEGF, iNOS, CD31, caspase-3 and Bax were also performed. UA significantly inhibited tumor growth, cell viability, in both ascites and solid tumor model in vivo (p < 0·001). The anti-angiogenic effects were accompanied with decreased VEGF, iNOS, TNF-α and increased IL-12 levels. UA at 100 mg/kg bw dose significantly increased SOD and CAT activity (p < 0.01). GSH and TBARS were increased as compared to control group (p < 0.001). Furthermore, UA increased total RBCs, WBCs as well as Hb% significantly (p < 0.05) compared to cyclophosphamide (CP). Histopathological examination of tumor cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. Decreased peritoneal angiogenesis showed the anti-angiogenic potential. UA downregulated VEGF & iNOS expression whereas bax and caspase-3 expressions were upregulated suggesting drug induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3 and downregulation of VEGF. The present study sheds light on the potent antitumor property of the UA and can be extended further to develop therapeutic protocols for treatment of cancer.     

Caspase信号通路在双歧杆菌脂磷壁酸诱导结肠癌细胞凋亡中的作用

目的探讨Caspase信号通路在双歧杆菌脂磷壁酸（LTA）诱导结肠癌细胞凋亡中的作用。方法RT-PCR检测经双歧杆菌LTA处理后,结肠癌Lovo细胞中MyD88和FADD mRNA的表达变化;AnnexinV检测经Caspase通用抑制剂（Z-Val-Ala-Asp-FMK）预先处理后,双歧杆菌LTA诱导结肠癌Lovo细胞凋亡率的变化;荧光法检测经双歧杆菌LTA处理后,Lovo细胞中Caspase-8活性的变化。结果经双歧杆菌LTA处理后,Lovo细胞中MyD88的mRNA表达明显升高（P〈0．05）,而FADD信号分子的mRNA表达无明显变化;双歧杆菌LTA能够增强Lovo细胞中Caspase-8的活性（P〈0．05）,且其诱导Lovo细胞凋亡的作用能够被Caspase抑制剂所抑制（P〈0．05）。结论MyD88信号分子在双歧杆菌LTA诱导Lovo细胞凋亡中可能起着承接上游分子TLRs与下游信号分子FADD的作用;而Caspase信号通路可能是双歧杆菌LTA诱导结肠癌Lovo细胞凋亡的主要信号传导途径。     

Dehydrotrametenolic acid selectively inhibits the growth of H-ras transformed rat2 cells and induces apoptosis through caspase-3 pathway

The screening of natural products that preferentially inhibit growth of H-ras transformed rat2 cells vs. rat2 cells was performed to identify H-ras specific growth inhibitor. A lanostane-type triterpene acid, dehydrotrametenolic acid (3beta-hydroxylanosta-7,9(11),24-trien-21-oic acid), was isolated from the sclerotium of Poria cocos (Polyporaceae). Dehydrotrametenolic acid selectively inhibited the growth of H-ras transformed cells with a GI(50) value of 40 microM. FACS analysis indicated that the compound exerted its anti-proliferation effects through cell cycle arrest at G2/M phase and accumulation of sub-G1 population. Dehydrotrametenolic acid-induced apoptosis was further confirmed with chromosomal DNA fragmentation, caspase-3 activation, and degradation of PARP and Lamin A/C degradation. The compound also regulated the expression of H-ras, Akt and Erk, which are the downstream proteins of H-ras signaling pathways. The results suggest that dehydrotrametenolic acid can be a potential anticancer agent against H-ras transformed tumor.     

大田软海绵酸对人胚胎羊膜细胞FL凋亡的影响

大田软海绵酸（Okadaic acid,OA）是一种C38的长链脂肪酸,属聚醚类海洋毒素,是腹泻性贝毒（Diarrhetic shellfish poisoning,DSP）的主要成分,化学结构见下图。最初从大田软海绵（Halichondria Okadai）和隐瓜海绵（H．melanodocia）中分离得到,后发现实际上是由共生于上述两种海绵的利马原甲藻（Prorocentrum lima）所产生。     

Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells

Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible cells. However, the signaling pathway of their apoptotic effects remains undefined. In this study, the cytotoxic effect of emodin on various human hepatoma cell lines was investigated. Results demonstrated that emodin exhibited strongly suppressing effect on HepG2/C3A, PLC/PRF/5, and SK-HEP-1 cells, with the IC(50) value of 42.5, 46.6, and 53.1 microM, respectively. Furthermore, emodin induced apoptosis in HepG2/C3A cells was clearly verified by the appearance of DNA fragmentation and sub-G(1) accumulation. Besides, HepG2/C3A cells were found to be arrested in G(2)/M phase after the cells were treated with 60 microM emodin for 48 h. Moreover, significant increase in the levels of apoptosis-related signals such as p53 (419.3 pg/ml), p21 (437.4 units/ml), Fas (6.6 units/ml), and caspase-3 (35.4 pmol/min) were observed in emodin treated HepG2/C3A cells. Taken together, emodin displays effective inhibitory effects on the growth of various human hepatoma cell lines and stimulates the expression of p53 and p21 that resulted in the cell cycle arrest of HepG2/C3A cells at G(2)/M phase. Results also suggest that emodin-induced apoptosis in HepG2/C3A cells were mediated through the activation of p53, p21, Fas/APO-1, and caspase-3. It implies that emodin could be a useful chemotherapeutical agent for treatment of hepatocellular carcinoma (HCC).     

The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis

We have identified a class of tau fragments inducing apoptosis in different cellular contexts, including a human teratocarcinoma-derived cell line (NT2 cells) representing committed human neuronal precursors. We have found a transition point inside the tau molecule beyond which the fragments lose their ability to induce apoptosis. This transition point is located around one of the putative caspase-3 cleavage sites. This is the only site that can be effectively used by caspase-3 in vitro, releasing the C-terminal 19 amino acids of tau. These results establish tau as a substrate for an apoptotic protease that turns tau itself into an effector of apoptosis. Accordingly, tau may be involved in a self-propagating process like what has been predicted for the pathogenesis of different neurodegenerative disorders.     

Mefenamic acid-induced apoptosis in human liver cancer cell-lines through caspase-3 pathway

Non-steroidal anti-inflammatory drugs (NSAIDs) have anti-proliferative effects and induce apoptosis in colon and other cancers. In the present study, we report that mefenamic acid (MEF), a member of NSAIDs, has an inhibitory effect on a proliferation of liver cancer cells. We used Chang and Huh-7 cells as human liver cancer cells. MEF-treated Huh-7 and Chang cells displayed apoptotic morphological changes and the portion of cells in sub G1 was increased 3-fold and 6-fold, respectively, at a 200 microM concentration. We also show an MEF-enhanced binding of annexin V to cells and an increased activity of caspase-3 to cleave PARP-1 and caspase itself. The inhibitor of caspase-3 blocked PARP-1 cleavage activity and protected against MEF-induced apoptotic cell death. These results indicate that MEF induces apoptosis in human liver cancer cells.