Bcl-2家族在冬凌草甲素诱导人多发性骨髓瘤细胞凋亡中的作用

目的探讨部分Bcl-2家族成员基因表达变化在冬凌草甲素（Ori）诱导人多发性骨髓瘤ARH-77细胞凋亡过程中的作用。方法采用MTT法和流式细胞术检测0ri作用后ARH-77细胞的活力和凋亡情况,相差显微镜观察细胞形态改变,RT-PCR法检测Bcl-2家族成员的基因表达变化。结果Ori能明显抑制ARH-77细胞的生长,且呈时间一剂量依赖性。10μmol／LOri作用于ARH-77细胞24h后可见细胞变小、胞质中出现空泡,并可见凋亡小体。流式细胞仪检测显示,细胞凋亡率随Ori作用时间的延长而逐渐增加（P〈0．05）。Ori诱导ARH-77细胞凋亡与Bcl-2、Bcl-xl、BaxmRNA水平改变有关（P〈0．05）。结论Ori能通过调节ARH-77细胞Bcl-2家族成员的表达而诱导其发生凋亡。     

Expression of Bcl-2 family modulated through p53-dependent pathway in human hepatocellular carcinoma

The biological behavior of hepatocellular carcinoma (HCC) is, in part, relevant to apoptosis. A systematic investigation of the apoptosis-related Bcl-2 family modulated by p53 in HCC is lacking. A total of 22 HCC patients were studied. The expression of p53 protein in HCC was assessed using the immunohistochemical method, which categorized the HCC patients into two groups: group 1, with immunonegative p53 (N = 7); and group 2, with immunopositive p53 (N = 15). The expression of p53, p21, Bcl-2, Bax, Bcl-x_L, and Bcl-x_S in the 22 HCC cases detected by western bioting was quantified with a densitometer. The apoptosis of the 22 HCC cases was determined by terminal deoxynucleotidyltransferase-mediated UTP end-labeling (TUNEL). We found that Bcl-2 was remarkably up-regulated in group 2 (14 of 15), but was down-regulated in group 1 (5 of 7). Bax was up-regulated in both group 1 (6 of 7) and group 2 (13 of 15). Bcl-x_L was up-regulated in both group 1 (5 of 7) and group 2 (9 of 15). Bcl-x_S was remarkably down-regulated in group 2 (14 of 15) compared to group 1 (4 of 7). The apoptosis indexes of groups 1 and 2 were 0.82±0.26% and 0.33±0.17%, respectively (P = 0.023). The long-term survival of group 1 was superior to that of group 2 (log-rank test, P = 0.001). In conclusion, Bcl-2 and Bcl-x_S represented the most significant anti- and proapoptotic proteins, respectively, modulated through a p53-dependent pathway in HCC.     

Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease

INTRODUCTION Liver steatosis results from triglyceride accumulation in hepatocytes in the course of many diseases[1]. The failure of energetic processes in hepatocytes leads to progressive lipid increase in cytoplasm[2]. The most common cause of liver ste…     

肾母细胞瘤经动脉化疗栓塞术疗效机制探讨

目的： 探讨肾母细胞瘤术前经动脉化疗栓塞的疗效机制。方法: 17例肾母细胞瘤患儿介入治疗后再行肿瘤切除，另 22例行单纯手术切除。对照分析2组肾母细胞瘤样本中细胞和间质的变化，采用原位细胞凋亡(TUNEL 法) 检测瘤细胞凋亡，并通过免疫组化法检测瘤细胞P53、Bcl-2 和Bax蛋白的表达。术后随访2年以上。结果: 介入组与单纯手术组的肿瘤坏死区域平均面积分别为60%、15 %（Uc = 2.84）；肿瘤组织呈X₃、X₄退变者分别为58.8%（10/17）和4.55%（1/22）（2c= 11.4）、间质纤维组织增生程度中、重度变化者分别为64.7%（11/17）和18.2%（4/22）（Uc = 2.72）、淋巴细胞侵润者分别为70.6%（12/17）和18.2%（4/22）（2c=10.9），2组有显著差异（P<0.01）；介入组肿瘤细胞分裂指数的中位数为0.2/10高倍视野，明显低于单纯手术组的1.4/10高倍视野（Uc = 54.50 ，P<0.01）；94.9(37/39)的病例中均有不同数量的阳性凋亡细胞出现。介入组肿瘤细胞凋亡指数的中位数为25.9/10高倍视野，明显高于单纯手术组的12.8/10高倍视野（Uc = 117.00，P<0.05）。P53和Bcl-2蛋白表达与瘤细胞凋亡及分化程度均无相关性（P>0.05），但Bax 蛋白在介入组瘤细胞表达率（80.0%）明显高于单纯手术组（40.0%），差异显著（P<0.05）。介入组2年无瘤生存率为73.3%（11/15），单纯手术组为42.9%（6/14）。结论: 经动脉化疗栓塞治疗能够有效杀伤肿瘤细胞、抑制肿瘤生长，诱导由Bax蛋白介导的肿瘤细胞凋亡。     

Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 expression (LMP1) is commonly found in the tumour cells. LMP1 has been shown to be involved in modulation of cell growth in B cells but the biological properties of LMP1 expression in nasopharyngeal carcinoma cells are less defined. In this study, a full length LMP1 gene was introduced into an EBV negative nasopharyngeal carcinoma cell line, CNE2, and five LMP1-expressing clones were isolated. Expression of LMP1 did not confer cell growth advantage in CNE2 cells; instead, it induced growth inhibition both in vitro and in vivo. In addition, the LMP1 transfected cells were more susceptible to cisplatin-induced cell death and showed 1.4-4.0-fold increased sensitivity to cisplatin compared to the vector infected control clones. The effect of LMP1 on the balance of Bcl-2 and Bax ratio may play a role in inducing susceptibility to cisplatin-induced cell death. These results demonstrated that LMP1 did not confer growth advantage in CNE2 cells, suggesting that expression of LMP1 may not be crucial in sustaining cell growth in established cell lines. Alternatively, LMP1 alone may not be sufficient to facilitate nasopharyngeal carcinoma cell growth and additional oncogenic factors may be needed along with LMP1 in modulating the malignant property of nasopharyngeal carcinoma.     

STAT3、 Bcl-xL、 Bax和CyclinD1在非小细胞肺癌中的表达

目的：分析STAT3、 Bcl-xL、 Bax和CyclinD1在非小细胞肺癌和正常肺组织中的表达及关系, 以进一步探讨其与非小细胞肺癌发生发展的关系.方法：利用SABC免疫组织化学技术检测84例非小细胞肺癌组织及30例正常肺组织中STAT3、 Bcl-xL、 Bax和CyclinD1的表达.结果：（1）STAT3、 Bcl-xL和CyclinD1在非小细胞肺癌组织中的表达水平明显高于正常肺组织（P＜0.05）, Bax在非小细胞肺癌组织有一定表达, 但与其在正常肺组织的表达比较无统计学意义（P＞0.05）;（2）STAT3、 Bcl-xL表达水平与非小细胞肺癌组织学类型有关, 在腺癌组织中的表达明显高于鳞癌, 与肿瘤大小、组织分化程度、 TNM分期及淋巴结转移无关;（3）Bax、 CyclinD1的表达水平与与组织学类型、肿瘤大小、组织分化程度、 TNM分期及淋巴结转移无关（P＞0.05）.结论：STAT3、 Bcl-xL和CyclinD1可能在肺癌的发生发展中发挥重要作用, 由此可望寻找到新的非小细胞肺癌的诊断方法和治疗靶点.     

Apoptosis of human pancreatic cancer cells induced by Triptolide

AIM： To investigate apoptosis in human pancreatic cancer cells induced by Triptolide （TL）, and the relationship between this apoptosis and expression of caspase-3＇ bcl-2 and bax. METHODS： Human pancreatic cancer cell line SW1990 was cultured in DMEM media for this study. MTT assay was used to determine the cell growth inhibitory rate in vitro. Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment. RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3＇ bcl-2 and bax. RESULTS： TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner. TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics. TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h, the apoptotic rates of human pancreatic cancer cells increased significantly. RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not. CONCLUSION： TL is able to induce the apoptosis in human pancreatic cancer cells. This apoptosis may be mediated by up-regulating the expression of apoptosisassociated caspase-3 and bax gene.     

大鼠血管性痴呆模型动物中海马神经元凋亡和蛋白表达的研究

目的:观察不同时点分别结扎左、右颈总动脉建立大鼠血管性痴呆模型中海马CA1区神经元凋亡和Bcl-2及Bax蛋白表达的影响,探讨其在血管性痴呆发病过程中的作用。方法:采取间隔3 d分2次结扎双侧颈总动脉建立血管性痴呆模型,术后4周用TUNEL法检测海马CA1区神经元凋亡,用免疫组织化学法检测其Bcl-2及Bax蛋白表达。结果:模型组大鼠海马CA1区可见大量凋亡神经元;模型组Bcl-2及Bax蛋白表达明显增加,与假手术组比较差异均有显著意义(P<0.05)。结论:此血管性痴呆模型大鼠中海马CA1区神经元大量凋亡丢失,可能是导致血管性痴呆的病理基础。     

培补肝肾方药对帕金森模型小鼠黑质内Bax和Bcl-2表达的影响

目的：观察培补肝肾方药对帕金森模型小鼠黑质内Bax和Bcl-2表达的影响,探讨此方药预防帕金森病的机制。方法：成年C57-BL雄性小鼠分为对照组、模型组和中药治疗组。应用免疫组织化学染色技术,观察各组小鼠黑质内Bax和Bcl-2表达的变化情况。结果：Bax和Bcl-2阳性神经元主要位于黑质致密部,其中Bax和Bcl-2阳性神经元的数量在对照组和中药治疗组均较少且组间无显著差异;MPTP造模后,Bax阳性神经元的数量随时间明显递增,Bcl-2阳性神经元的数量亦呈逐渐递增的趋势。结论：培补肝肾方药可能通过抑制黑质神经元内Bax基因表达的途径抑制黑质神经元的凋亡,从而对帕金森病发挥预防和治疗作用。     

黄连素对人胃癌细胞SGC7901凋亡影响的研究

目的:探讨黄连素对人胃癌细胞SGC7901凋亡的影响。方法:MTS法检测不同浓度的黄连素(100、150、200μmol/L)对胃癌细胞的抑制作用,Hoechst 33258染色检测不同浓度的黄连素(100、150、200μmol/L)对细胞凋亡的影响;Real Time Q-PCR检测胃癌细胞中Cleaved Caspase-3、Bcl-2、Bax的mRNA表达;Western blot检测胃癌细胞中Cleaved Caspase-3、Bcl-2、Bax的蛋白表达。结果:不同浓度的黄连素能显著降低人胃癌细胞SGC701活性(P<0.05,P<0.01),促进其凋亡,升高Cleaved Caspase-3、Bax的mRNA和蛋白表达水平(P<0.05,P<0.01),降低Bcl-2的mRNA和蛋白表达水平(P<0.05,P<0.01)。结论:不同浓度的黄连素可诱导胃癌细胞凋亡,其机制可能与升高Cleaved Caspase-3、Bax的表达,降低Bcl-2的表达有关。