替尼泊甙和羟基喜树碱对胃癌BGC-823细胞增殖和凋亡的作用

背景与目的:研究显示,拓扑异构酶(topoisomerase,Topo)Ⅰ和Ⅱ抑制剂联合应用有一定的协同抗肿瘤作用,但两物联合应用治疗胃癌的报道较少.本研究探讨Topo Ⅰ抑制剂羟基喜树碱(hydroxycamptothecin,HCPT)和TopoⅡ抑制剂替尼泊甙(teniposide,VM-26)联合应用对胃癌细胞BGC-823的体外抑制作用和诱导细胞凋亡的作用.方法:利用噻唑蓝(MTT)法测定HCPT、VM-26单药及联合用药对BGC-823细胞的体外抑制作用,流式细胞仪测定细胞凋亡.结果:1.963～31.413 μmol/L VM-26对BGC-823细胞的抑制率为15.99%～80.83%;1.963 μmol/LVM-26处理细胞0、12、24、48 h,细胞凋亡率分别为3.90%、4.42%、7.60%、17.70%.8.577～137.227 μmol/L HCPT对细胞的抑制率为7.89%～70.32%,8.577 μmol/LHCPT处理0、12、24、48 h后,细胞凋亡率分别为2.80%、8.50%、10.50%、13.30%.联合用药时抑制率为21.32%～87.74%,凋亡率为2.80%、15.50%、15.70%、20.20%.联合用药指数为1.293.结论:HCPT与VM-26单药可抑制BGC-823细胞增殖,诱导细胞凋亡;HCPT与VM-26联合应用在胃癌细胞中产生拮抗作用.

Effects of hydroxycamptothecin and teniposide on proliferation and apoptosis of gastric cancer cell line BGC-823

BACKGROUND & OBJECTIVE: Some studies have showed that topoisomerase (Topo)I and II inhibitors have synergistic effects in tumor therapy, but the combinations have seldom been used in gastric cancer. This study was to investigate the effects of Topo I inhibitor hydroxycamptothecin (HCPT) and Topo II inhibitor teniposide (VM-26) on the proliferation and apoptosis of gastric cancer cell line BGC-823. METHODS: MTT assay was used to examine the inhibitory effects of VM-26 and HCPT, used alone or in combination, on the proliferation of BGC-823 cells. Cell apoptosis was examined by flow cytometry (FCM). RESULTS: The inhibition rates of BGC-823 cell proliferation were 15.99%-80.83% when treated with 1.963-31.413 micromol/L VM-26; the apoptosis rates were 3.90%, 4.42%, 7.36%, 17.07% when exposed to 1.963 micromol/L VM-26 for 0, 12, 24, 48 h, respectively. The inhibition rates of BGC-823 cell proliferation were 7.89%-70.32% when treated with 8.577-137.227 micromol/L HCPT; the apoptosis rates were 2.80%, 8.50%, 10.50%, 13.30% when exposed to 8.577 micromol/L HCPT for 0, 12, 24, 48 h, respectively. When treated with 1.963 micromol/L VM-26 and 3.125 microg/ml HCPT for 0, 12, 24, 48 h, the inhibition rates of BGC-823 cell proliferation were 21.32%-87.74%, and the apoptosis rates were 2.80%, 15.50%, 15.70%, 20.20%, respectively. The combination index (CI) was 1.293. CONCLUSION: HCPT and VM-26 used alone could inhibit the proliferation and induce the apoptosis of BGC-823 cells, and they have antagonistic effect on gastric cancer BGC-823 cells.