Nanjing Chest Hospital, South-east University Clinical Medical School, Nanjing 210009, Jiangsu Province, China.
Biomed Pharmacother. 2011 Jun;65(3):137-41. doi: 10.1016/j.biopha.2010.12.001. Epub 2010 Dec 30.
Lobaplatin, as the third-generation platinum antineoplastic agent, showed promising antineoplastic effects in variety of preclinical test tumor models. We investigated the inhibition effect of lobaplatin on the colorectal carcinoma cell line LOVO in vitro, and explored its mechanism of action. The MTT assay was used to determine the inhibitory effect and inhibition ratio of lobaplatin on LOVO at various lobaplatin concentrations (500 μM, 1000 μM, 2000 μM). Apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP nickend labelling (TUNEL). The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3,8,9 in cells was detected by chromometry. The results of MTT assay showed that proliferation of LOVO cells was inhibited by lobaplatin in a concentration-dependent manner. Apoptosis was detected in LOVO cells by TUNEL. The FCM assay indicated that lobaplatin altered the cell cycle and induced apoptosis of the LOVO cells when treated for 24h, the percentages of cells in the S phase transition were increased, whereas the percentages of cells in the G(2) transition were decreased. The expressions of caspase-389 is higher than the control group after LOVO cells were treated by lobaplatin. Lobaplatin can inhibit the proliferation of colorectal carcinoma cell line LOVO by inducing apoptosis in vitro. The mechanism may be related to the "S" cycle arrest in cell cycle distribution and the up-regulated expression of caspase-8 and caspase-9 which up-regulated the expression of caspase-3.
洛铂作为第三代铂类抗肿瘤药物,在多种临床前测试肿瘤模型中显示出良好的抗肿瘤作用。我们研究了洛铂对体外结直肠癌细胞 LOVO 的抑制作用,并探讨了其作用机制。MTT 法测定不同浓度洛铂(500μM、1000μM、2000μM)对 LOVO 的抑制作用及抑制率。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法(TUNEL)检测细胞凋亡。流式细胞术(FCM)分析细胞周期和凋亡率,显色法检测细胞中 caspase-3、8、9 的表达。MTT 结果显示,洛铂对 LOVO 细胞的增殖呈浓度依赖性抑制。TUNEL 检测到 LOVO 细胞发生凋亡。FCM 检测结果表明,洛铂作用 24h 后可改变细胞周期,诱导 LOVO 细胞凋亡,S 期细胞百分比增加,G2 期细胞百分比减少。与对照组相比,洛铂处理 LOVO 细胞后 caspase-3、8、9 的表达均升高。洛铂可通过诱导细胞凋亡抑制结直肠癌细胞 LOVO 的增殖。其机制可能与细胞周期分布中“s”期阻滞和 caspase-8、caspase-9 表达上调,从而上调 caspase-3 的表达有关。