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.