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目的研究去乙酰化转移酶抑制剂TSA对人胰腺癌PANC-1细胞生长的影响及其作用机制。方法用不同浓度的TSA处理PANC-1细胞。MTT法检测肿瘤细胞的增殖;流式细胞仪分析细胞凋亡及细胞周期;Western免疫印迹及荧光定量RT-PCR分析抗凋亡基因bcl-2和肿瘤抑制基因p21WAF1/CIP1的表达。结果TSA作用于PANC-1细胞能明显抑制细胞的增殖,且具有明显的剂量依赖性;TSA处理72 h的PANC-1细胞其早期凋亡率明显提高(P<0.05),G0/G1期细胞比例显著升高(P<0.05),S期细胞比例显著降低(P<0.05)。TSA在转录和翻译水平上能明显下调bcl-2的表达(P<0.05),上调p21WAF1/CIP1的表达(P<0.05)。结论TSA可以通过诱导胰腺癌细胞的凋亡和周期阻滞而抑制癌细胞生长;其发生机制可能与下调抗凋亡基因bcl-2和上调肿瘤抑制基因p21WAF1/CIP1的表达有关。
Objective To study the effect and mechanism of deacetylase (TSA) inhibitor TSA on the growth of human pancreatic cancer PANC-1 cells. Methods PANC-1 cells were treated with different concentrations of TSA. The proliferation of tumor cells was detected by MTT assay. Apoptosis and cell cycle were analyzed by flow cytometry. The expressions of anti-apoptotic gene bcl-2 and p21WAF1 / CIP1 were detected by Western blotting and quantitative RT-PCR. Results TSA treatment of PANC-1 cells significantly inhibited cell proliferation in a dose-dependent manner. The apoptosis rate of PANC-1 cells treated with TSA for 72 h was significantly increased (P <0.05), while cells in G0 / G1 phase (P <0.05), and the proportion of cells in S phase was significantly decreased (P <0.05). TSA significantly down-regulated the expression of bcl-2 (P <0.05) and p21WAF1 / CIP1 (P <0.05) at transcription and translation levels. Conclusion TSA can inhibit the growth of cancer cells by inducing the apoptosis and cell cycle arrest of pancreatic cancer cells. The mechanism may be related to the down-regulation of anti-apoptotic gene bcl-2 and the upregulation of the tumor suppressor gene p21WAF1 / CIP1.