Fudan University, Liver Cancer Institute and Zhongshan Hospital, 136 Yi Xue Yuan Road, 200032 Shanghai, PR China.
Expert Opin Investig Drugs. 2009 Nov;18(11):1595-604. doi: 10.1517/13543780903292626.
The platinum-based chemotherapeutic agent oxaliplatin displays a wide range of antitumor activities. To date, no detailed data are available about the effects of oxaliplatin on hepatocellular carcinoma (HCC) cells. Herein, the anti-proliferation effects of oxaliplatin on HCCLM3 and Hep3B cells in vitro and in vivo are studied.
Cell viability was assessed by an MTT assay and apoptosis by flow cytometry and transmission electron microscopy. Apoptosis-related proteins in HCCLM3 cells were evaluated by microarray analysis, quantitative reverse transcriptase-PCR assay and western blotting. The effect of oxaliplatin was also studied in vivo using a xenograft model.
Oxaliplatin inhibited the growth of HCCLM3 and Hep3B cells. Using flow cytometry, transmission electron microscopy and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, we found that apoptosis was the main mechanism by which oxaliplatin inhibited tumor progression. Microarray analysis, quantitative reverse transcriptase-PCR and western blot analysis further demonstrated downregulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL and upregulation of the pro-apoptotic protein Bax during oxaliplatin-induced apoptosis.
The anti-proliferation effect of oxaliplatin in HCC cells is due to induction of apoptosis. Therefore, oxaliplatin may be an effective treatment for HCC and its use merits further in-depth investigation.
铂类化疗药物奥沙利铂具有广泛的抗肿瘤活性。迄今为止，尚无关于奥沙利铂对肝细胞癌（HCC）细胞影响的详细数据。本研究旨在研究奥沙利铂在体外和体内对 HCCLM3 和 Hep3B 细胞的抗增殖作用。
通过 MTT 法评估细胞活力，通过流式细胞术和透射电子显微镜评估细胞凋亡。通过微阵列分析、定量逆转录酶 -PCR 检测和 Western blot 评估 HCCLM3 细胞中与细胞凋亡相关的蛋白。还使用异种移植模型研究了奥沙利铂的作用。
奥沙利铂抑制 HCCLM3 和 Hep3B 细胞的生长。通过流式细胞术、透射电子显微镜和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法，我们发现细胞凋亡是奥沙利铂抑制肿瘤进展的主要机制。微阵列分析、定量逆转录酶 -PCR 和 Western blot 分析进一步表明，奥沙利铂诱导细胞凋亡时，抗凋亡蛋白 Bcl-2 和 Bcl-xL 下调，促凋亡蛋白 Bax 上调。
奥沙利铂在 HCC 细胞中的抗增殖作用是由于诱导细胞凋亡所致。因此，奥沙利铂可能是治疗 HCC 的有效方法，值得进一步深入研究。
