Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth

Abstract

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.

Keywords::

• apoptosis
• Bcl-2 family
• hepatocellular carcinoma
• oxaliplatin

Acknowledgement

Z Wang & J Zhou contributed equally to this work.

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