Characterization of drug and radiation sensitivity mechanisms in human hepatocellular carcinoma Hep G2 cells after fractionated gamma-irradiation

Liver cancer is one of the major types of cancer in Hong Kong. The treatment of liver cancer includes chemotherapy, radiotherapy and surgery. Although surgery is the most common form of treatment for liver cancer, the unresectable liver cancer is mostly treated by chemo- or radiotherapy. The failure of radiotherapy and chemotherapy is usually associated with the development of radiation resistance and drug resistance in cells. In clinical practice, radiation such as X-rays or gamma rays, is usually administered as daily fractions. It is known as fractionated radiotherapy. It has been observed that some patients who have previously undergone radiotherapy have a lower rate of response to subsequent chemotherapy and radiotherapy. However, there were only a few cellular models available to study the relationship between radiation resistance and drug resistance in those liver cancer cells survived from treatment of radiation.; In the present study, two sublines of human hepatocellular carcinoma Hep G2 cells were established by exposing cells to two different irradiation regimes (137 Cesium gamma radiation), 2 Gy for 10 days or 10 Gy for 2 days, respectively. Their drug and radiation sensitivity were then examined. Compared to parent cells, radiation conditioned Hep G2 cells were found to be more resistant to radiation, more sensitive to doxorubicin (DOX), taxol (TAXOL) and vincristine (VCR) but had similar sensitivity to cisplatin (CP) and etoposide (EP).; By using Western blot analysis, Northern blot analysis, RT-PCR based differential display and cDNA microarray, the gene expression profile between radiation conditioned Hep G2 cells and parent cells were compared. Among the genes identified to demonstrate differential expression between parent and radiation conditioned cells, the molecules in Raf-1 signaling pathway are believed to contribute radiation resistance in cells. However, the sensitivity to DOX and the anticancer drugs is suggested to be correlated with drug induced apoptosis. The results from the present study suggested that cells survived from radiation therapy have alteration of their response to drug and radiation.