Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth
- Expert Opin Investig Drugs. 2009 Nov;18(11):1595-604. doi: 10.1517/13543780903292626.
- 1. Fudan University, Liver Cancer Institute and Zhongshan Hospital, 136 Yi Xue Yuan Road, 200032 Shanghai, PR China.
Objective: 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.
Research methods: 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.
Results: 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.
Conclusions: 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.