G2/M perturbations with paclitaxel and radiation cause cytotoxicity in HepG2 hepatocellular carcinoma cells: Implications for developing therapies

We used a cell line model to analyze whether G2/M perturbations could cause cytotoxicity in hepatocellular carcinoma (HCC). Studies were conducted with paclitaxel and radiation. Cell viability assays showed that the IC50 of paclitaxel was 19 nM. This IC50 of paclitaxel decreased to 6 nM when HepG2 cells were treated with radiation. Flow cytometry showed that cells accumulated in G2/M following paclitaxel and radiation treatment, with >50% in G2/M following treatment with paclitaxel and radiation in combination. Exposure to paclitaxel and radiation increased apoptosis rates in HepG2 cells, although nonapoptotic cell death was more frequent. The colony-forming ability of HepG2 cells decreased in vitro after treatment with paclitaxel and radiation. Similarly, tumor-forming ability of HepG2 cells was decreased in immunodeficient animals treated with paclitaxel. These findings indicate that analysis of mechanisms inducing G2/M lesions will be helpful for developing treatments for HCC.