Differential paclitaxel-induced cytotoxicity in rodent and human hepatoma cell lines

Hepatoma is the leading cause of death in male cancer patients in Taiwan. In this study, we examined the effect of Paclitaxel on the in vitro growth of 2 rodent and 4 human hepatoma cell lines. Differential Paclitaxel-induced cytotoxicity was observed among hepatoma cell lines. In Paclitaxel-sensitive Hep3B and N1S1 cells, Paclitaxel-induced cytotoxicity was dose- and time-dependent. The effective doses of Paclitaxel were in the range 0.1-1.0 microM. Flow cytometric analysis showed that Paclitaxel-treated hepatoma cells were arrested in G2-M phases prior to apoptosis. In addition, growth inhibition by Paclitaxel was accompanied by an increase in the expression of proliferating cell nuclear antigen (PCNA) in hepatoma cells. For Paclitaxel-resistant hepatoma cells, cytostatic response and/or polyploidization was observed. Our results indicated that two thirds of the hepatoma cell lines examined showed some degree of resistance to Paclitaxel treatment in vitro. The expression of p53 gene had no direct effect on Paclitaxel-induced cytotoxicity. The expression of PCNA and the development of polyploidization appear to be good markers for measuring Paclitaxel response. These findings suggest that Paclitaxel alone appears to by cytostatic to hepatoma cells, combination of Paclitaxel with other chemotherapeutic agents may show better cytotoxic effects.