Human hepatoma is a vicious cancer, widespread in Asia, which does not respond to traditional therapies. Recent researches have indicated that through manipulating the regulators of apoptosis such as the members of the Bcl-2 family, the chemosensitivity of cancer cells could be changed. The objective of this research is through studying the role of Bcl-2 family proteins in apoptosis of human hepatoma cell lines, to explore whether manipulation of Bcl-2 family members can make human hepatoma cells more sensitive to chemotherapeutic agents....[ Read more ]

Human hepatoma is a vicious cancer, widespread in Asia, which does not respond to traditional therapies. Recent researches have indicated that through manipulating the regulators of apoptosis such as the members of the Bcl-2 family, the chemosensitivity of cancer cells could be changed. The objective of this research is through studying the role of Bcl-2 family proteins in apoptosis of human hepatoma cell lines, to explore whether manipulation of Bcl-2 family members can make human hepatoma cells more sensitive to chemotherapeutic agents.

In the present study, we used the chemotherapeutic agents taxol and doxorubicin to induce apoptosis in human hepatocellular carcinoma cell line QGY-7703 and hepatoblastoma cell line HepG2. Investigation of the expression profile of Bcl-2 family proteins in both cell lines show that different expression profiles exist between QGY-7703 and HepG2 cells, e.g. QGY-7703 is Bcl-2, Bax, Bcl-XL, Bak and Bad positive, while HepG2 is Bcl-XL, Bak and Bad positive, but Bcl-2 and Bax negative. Expression patterns of Bcl-2 farnily proteins are also different during the apoptotic process triggered by taxol and doxorubicin in these two cell lines, e.g. taxol causes phosphorylation of Bcl-2 protein in QGY-7703 cells; both taxol and doxorubicin cause down-regulation of Bad protein in HepG2, but not in QGY-7703 cells.

Our observations in gene transfection experiments indicate that Bcl-2 protein levels are directly proportional to the resistance of QGY-7703 cells to chemotherapeutic agents taxol and doxorubicin. However, the sensitivity to taxol and doxorubicin of HepG2 cells, which are Bcl-2 and Bax negative, is independent of Bcl-2 levels. Bcl-XL gene transfection experiment in HepG2 cells indicates that lower Bcl-XL levels cause HepG2 cells to be more sensitive to taxol and doxorubicin.

These fmdings suggest that among the Bcl-2 family members, Bcl-2 and Bax may be the critical proteins in the regulation of apoptosis in QGY-7703 cells, while Bcl-XL and Bak may be the major regulators of apoptosis in HepG2 cells. The observation obtained from M-2 gene transfection experiment performed in HepG2 cells supports the previous notion that without Bax, Bcl-2 loses its apoptosis-inhibiting function.

The above observations also suggest that manipulation of Bcl-2 or Bcl-XL may be an effective approach to increase the chemosensitivity of human hepatoma cells, thereby improving the efficiency of hepatoma therapy. The present in vitro study provides the rationale for further exploration in vivo to increase chemosensitivity of human hepatoma through manipulation of Bcl-2 family members.