Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth.
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.


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.
Fudan University, Liver Cancer Institute and Zhongshan Hospital, 136 Yi Xue Yuan Road, 200032 Shanghai, PR China.
Zheng
Z
Wang
Jian
J
Zhou
Jia
J
Fan
Shuang-Jian
SJ
Qiu
Yao
Y
Yu
Xiao-Wu
XW
Huang
Jian
J
Sun
Chang-Jun
CJ
Tan
Zhi
Z
Dai
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics; D051020:bcl-X Protein / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000077150:Oxaliplatin