title: Protective effects of hepatic stellate cells against cisplatin-induced apoptosis in human hepatoma G2 cells.
abstract: The effects of hepatic stellate cells (HSCs) on tumorigenicity of HCC have been previously reported. However, the detailed mechanisms responsible for these effects remain unclear. In this study, we investigated the effects of HSCs on cisplatin-induced apoptosis in human hepatoma HepG2 cell lines. HepG2 cells were treated with cisplatin alone or co-cultured with LX-2 cells 3 days before incubation with cisplatin. Cisplatin causes apoptosis in HepG2 cells and LX-2 cells protect HepG2 cells from death. The protection of LX-2 cells against cisplatin-induced cytotoxicity in HepG2 cells appeared to be related to the inhibition of apoptosis, as determined by cytotoxicity assay and nuclear staining analysis. p53 and Bax mRNA levels were elevated, and cell cycle arrest was produced after cisplatin treatment. LX-2 cells suppressed this elevation of p53 and Bax as well as the cell cycle arrest induced by cisplatin, when compared with those of the treated cells with cisplatin alone. The LX-2 cells pretreatment inhibited the cisplatin-induced apoptosis, which was related with the incomplete blockage in p53 activation. In summary, the results of our present study demonstrate that HSCs protect HepG2 cells against cisplatin-induced apoptosis and its protective effects occur via inhibiting the activation of p53, which is of critical importance for enhanced understanding of fundamental cancer biology.
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Science, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Storr Liver Unit at the Westmead Millennium Institute, the University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Surgical Oncology, the First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Yongxun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Yucai
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D059016:Tumor Microenvironment; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002945:Cisplatin