Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or Bcl-2

作者：Wu GS; ElDeiry WS

来源：Clinical Cancer Research, 1996, 2(4): 623-633.

p53 has been implicated as a determinant of chemosensitivity and radiosensitivity, We measured chemosensitivity of human tumor cell lines (n = 11), with or without wildtype p53, following exposure to clinically useful chemotherapeutic drugs (n = 4). Chemosensitivity and apoptosis induction were correlated independently of p53 status or Bcl-2 protein levels in vitro. Wild-type p53 correlated with chemosensitivity in ovarian carcinoma and some Burkitt's lymphoma cells, but not in leukemia or lung cancer, Bcl-2 levels correlated with chemoresistance only in Burkitt's lymphoma, p53-dependent p21(WAF1/CIP1) induction and cell cycle arrest occurred at sublethal doses of chemotherapy, whereas at lethal doses of chemotherapy apoptotic death was observed, consistent with models proposing a relationship between the level of DNA damage versus survival or death, Loss of apoptosis induction was observed in drug-resistant ML-1 and HL-60 leukemia cells, without changes in p53 or Bcl-2. Targeted loss of p53 protein in H460 lung cancer cells using HPV-16 E6 inhibited the etoposide-induced G(1) checkpoint but did not decrease chemosensitivity, Our studies suggest that the simple measurement of apoptosis induction may be a useful predictor of chemosensitivity, at least in vitro, and confirm that p53 status and Bcl-2 expression may be useful predictors of chemosensitivity in certain cell types.

• 出版日期1996-4