塞来昔布对高表达Her-2-neu的人乳腺癌SKBr3细胞增殖及凋亡的影响.docVIP

塞来昔布对高表达Her-2/neu的人乳腺癌SKBr3细胞增殖及凋亡的影响 【摘要】 目的 探讨环氧合酶-2(COX-2)抑制剂塞来昔布对人乳腺癌细胞SKBr3的抑制增殖及诱导凋亡作用。方法 4种不同浓度的塞来昔布处理乳腺癌细胞系SKBr3细胞24、48 h，MTT法测定24、48 h后SKBr3细胞的增殖活性，流式细胞仪(FCM)检测48 h后各浓度塞来昔布诱导细胞凋亡情况及对细胞周期的影响。结果 与对照组相比，塞来昔布以时间、剂量依赖性方式抑制SKBr3细胞增殖(P0.05)。作用48 h后，塞来昔布诱导SKBr3细胞凋亡并阻断了细胞周期进展，凋亡率随塞来昔布浓度的增加而增加(P0.05)，且随着药物浓度的增加，G0/G1期细胞比例逐渐增加、S期及G2/M期细胞比例逐渐下降(P﹤0.05)。结论 塞来昔布抑制高表达Her-2/neu的SKBr3细胞的增殖，诱导其凋亡。 【关键词】 塞来昔布;乳腺癌;SKBr3细胞;增殖;凋亡 　　Abstract: Objective To investigate the antitumor effects of celecoxib-a cyclooxysenase-2 (COX-2) inhibitor on inhibiting proliferation and inducing apoptosis of Her2/neu-overexpressing human breast cancer cell line SKBr3. Methods Human breast cancer cell line SKBr3 cells were treated with celecoxib for 24 h and 48 h at 4 different concentrations, respectively. The proliferative activity was determined at the two time points by MTT assay and the effect of 4 concentrations of celecoxib on apoptosis induction and cell cycle of SKBr3 cells were detected by flow cytometry. Results Compared with the control group, celecoxib significantly inhibited the proliferation of SKBr3 cells in a dose-and time-dependent manner (P0.05). 48 h after treatment, celecoxib induced the apoptosis of the cells and blocked the progress of SKBr3 cell cycle; with the rise of celecoxib concentration, the apoptotic rate increased (P0.05), the SKBr3 cell proportion in G0/G1 cycle also gradually increased, while SKBr3 cell proportion in cycles S and G2/M gradually decreased (P0.05). Conclusion Celecoxib can inhibit the proliferation of SKBr3 cells overexpressing Her-2/neu and induce the cell apoptosis. 　　Key words： celecoxib; breast cancer; SKBr3 cell; proliferation; apoptosis 　　乳腺癌是女性最常见的恶性肿瘤之一，目前我国乳腺癌发病率呈明显上升趋势。20%～30%的乳腺癌患者Her-2/neu原癌基因高表达，阳性表达Her-2/neu者恶性程度高，病情进展迅速，预后不良[1]。因此，针对Her-2/neu靶向 治疗 的研究是近几年持续研究的热点。塞来昔布(celecoxib,西乐葆)是第一个用于临床的环氧合酶-2(COX-2)选择性抑制剂，在肿瘤治疗中的作用受到愈加广泛的关注。研究发现塞来昔布可抑制多种肿瘤细胞增殖，诱导其分化成熟及凋亡，且对正常细胞无明显毒副作用[2]。本实验研究塞来昔布对高表达Her-2/neu的乳腺癌细胞株SKBr3细胞增殖及凋亡的影响，并进一步分析其可能