Combination chemotherapy of doxorubicin and paclitaxel for hepatocellular carcinoma in vitro and in vivo

Abstract

Systemic combination chemotherapy is the only option for patients with unresectable hepatocellular carcinoma (HCC) not suitable for intra-arterial treatment. However, no systemic chemotherapy has been able to provide durable remission. The search for a new combination of drugs for HCC is significant. The combination of doxorubicin and paclitaxel shows promise in breast cancer therapy. This study was carried out to determine the synergistic effect of combined doxorubicin and paclitaxel in the two HCC cell lines: HepG2 and Huh7 in vitro and murine HCC H22-bearing BALB/c mice in vivo. The morphology of the two cell lines treated with drugs was photomicrographed. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay was used to determine the number of surviving cells. Cell cycle was evaluated by flow cytometry. Cell viability was measured by the ability of single cells to form colonies in vitro. Anti-tumor activities against subcutaneoulsy implanted solid tumor induced by H22 cells in mice were evaluated. Our data demonstrated that the cytotoxicity produced by doxorubicin and paclitaxel was additive in HCC cells, while it was mainly held in the G2/M phase of the cell cycle by paclitaxel. In vivo anti-tumor activity assay also showed that the combination of the two drugs resulted in more significant tumor regression, compared to the single one. The study may provide a new combination of cytotoxic drugs for HCC chemotherapy.