Co‐transduction of Apaf‐1 and Caspase‐9 Augments Etoposide‐induced Apoptosis in U‐373MG Glioma Cells

Several apoptosis‐related genes have been reported to be involved in chemotherapy‐induced apoptosis in cancers. An assessment of the relationship between expression of those genes and the degree of chemotherapy‐induced apoptosis may be useful in improving the efficacy of cancer therapy. We transduced Apaf‐1 (apoptotic protease‐activating factor‐1) and caspase‐9 into U‐373MG glioma cells using adenovirus (Adv) vectors in the presence of etoposide and evaluated the degree of apoptosis. The degree of apoptosis in etoposide‐treated U‐373MG cells infected with Adv for Apaf‐1 (Adv‐APAFl) was higher (27%) than that in cells infected with control Adv (14%), that in cells infected with Adv for caspase‐9 (Adv‐Casp9) was higher (34%) than that in cells infected with Adv‐APAFl, and that in cells infected with both Adv‐APAFl and Adv‐Casp9 was the highest (41%). Treatment with etoposide increased expression of p53 and decreased expression of Bcl‐X(L) in U‐373MG cells which harbored mutant p53. These results indicate that the expression of Apaf‐1 and caspase‐9 may be important determinants in predicting the sensitivity of cancers to chemotherapy. Adv‐mediated co‐transduction of Apaf‐1 and caspase‐9 should render cancer cells highly sensitive to chemotherapy.