奥沙利铂对人结肠癌细胞LoVo和SW480/M5作用的实验研究  

Effect of oxalioplatin on human colorectal cancer cell line LoVo and cell subline SW480 / M5

作　　者：吕会增[1] 魏波[2] 陈图峰[2] 苏雁甜 叶小勇[1] 陈新岐[1] 卫洪波[2] 

机构地区：[1]广州医学院第五附属医院普通外科,广州510700 [2]中山大学附属第三医院胃肠外科

出　　处：《消化肿瘤杂志（电子版）》2012年第1期34-39,共6页Journal of Digestive Oncology(Electronic Version)

基　　金：广州医学院博士启动基金资助项目(编号20100136)

摘　　要：目的探讨体外实验奥沙利铂对人结肠癌LoVo和SW480/M5细胞的抑制作用及其可能机制。方法 MTT法检测不同剂量奥沙利铂对LoVo和SW480/M5细胞增殖的抑制作用。流式细胞仪检测1/2GI_(50)和GI_(50)浓度奥沙利铂对LoVo和SW480/M5细胞周期和早期凋亡的影响。原子光谱吸收仪检测GI_(50)浓度奥沙利铂作用4、8、24h后LoVo和SW480/M5细胞DNA含铂量。结果奥沙利铂对LoVo和SW480/M5细胞增殖的抑制作用呈量效依赖;其GI_(50)浓度:LoVo细胞为6.5mg/L,SW480/M5细胞为58.0mg/L。自然对数增殖周期,LoVo细胞中G_1期细胞比例高于、G_2期细胞比例低于SW480/M5细胞(P<0.05)。奥沙利铂浓度GI_(50)时,降低肿瘤细胞G_1期比例,升高LoVo细胞S期比例较SW480/M5细胞明显,升高SW480/M5细胞而降低LoVo细胞G_2/M期比例。1/2GI_(50)、GI_(50)奥沙利铂均可诱导两种肿瘤细胞发生早期凋亡,但1/2GI_(50)L-OHP促凋亡作用两种肿瘤细胞间无统计学差异,GI_(50)L-OHP对LoVo细胞的促凋亡作用高于SW480/M5细胞。GI_(50)L-OHP奥沙利铂使两种肿瘤细胞DNA含铂量显著升高,并呈时效依赖。LoVo细胞DNA交联铂原子能力高于SW480/M5细胞。结论奥沙利铂主要通过阻滞细胞于S期或(和)G_2/M期并诱导细胞凋亡而抑制两种肿瘤细胞增殖。LoVo细胞对奥沙利铂敏感性明显高于SW480/M5细胞。Objective To investigate the inhibitory effect of oxalioplatin (L-OHP) on human colorectal cancer cell line LoVo and cell subline SW480 / M5 , and its possible mechanisms. Methods The inhibitory effect of L-OHP at different doses on LoVo and SW480 / M5 cells was determined by MTT assay. Cell cycle and cell apoptosis of both cell lines that were wild or treated with L-OHP at 1 / 2GI_(50) and GI_(50) concentrations were determined by flow cytometry. The Pt-DNA adducts of both cell lines treated with L-OHP at GI_(50) dose for different times were detected by atomic absorption spectrometry. Results L-OHP inhibited proliferation of both LoVo and SW480 / M5 cell lines in a dose-dependent manner. The GI_(50) of LoVo cells was 6.5 mg / L, while that of SW480 / M5 cells was 58.0 mg / L. In wild types , the percentage of G_1 -phase cells was significantly higher , and that of G_2 -phase cells was lower in LoVo cells than those in SW480 / M5 cells. GI_(50) L-OHP decreased the percentage of G_1 -phase cells, increased the percentage of S-phase cells, significantly more in LoVo cells than those in SW480 / M5 cells. GI_(50) L-OHP decreased the percentage of G_2 -phase cells in LoVo cells, but decreased that in SW480 / M5 cells. L-OHP at 1 / 2 GI_(50) or GI_(50) concentration induced apoptosis of both cell lines. There was no significant difference inimprovement of apoptosis induced by 1 / 2 GI_(50) L-OHP, but significant difference in such improvement of apoptosis induced by GI_(50) L-OHP, between the two cell lines. GI_(50) L-OHP increased the levels of Pt-DNA adducts in both cell lines in a time-dependent manner. The capacity of Pt-DNA adducting in LoVo cells was significantly higher than that in SW480 / M5 cells. Conclusions L-OHP can inhibit the growth of both L-OHP and SW480 / M5 cells by blocking the cells into S-phase or (and G_2 -phase) and inducing apoptosis. LoVo cells are more sensitive to L-OHP than SW480 / M5 cells.

关 键 词：奥沙利铂 人结肠癌细胞LoVo 细胞亚系SW480/M5 药物敏感性 

分 类 号：R735.35[医药卫生—肿瘤]