Anticancer research · 2002
Reduced expression of p53 and p21WAF1/CIP1 sensitizes human breast cancer cells to paclitaxel and its combination with 5-fluorouracil.
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Johnson Korey R, Fan Weimin
Аннотация
BACKGROUND: The favorable clinical activity of paclitaxel has prompted considerable interest in combining this agent with other clinically effective antineoplastic agents including the antimetabolite 5-fluorouracil (5-FU). Our previous studies indicated that simultaneous exposure or pretreatment with 5-FU could significantly interfere with the cytotoxic effects of paclitaxel on both mitotic arrest and apoptosis. Biochemical examination also revealed that 5-FU inhibited expression of p21WAF1/CIP1 that may contribute to paclitaxel cytotoxicity.
MATERIALS AND METHODS: In this study, human breast cancer BCap37 cells were transfected with either sense or antisense p53 or p21WAF1/CIP1. The established stable transfectants were then analyzed for an altered sensitivity to paclitaxel, 5-FU or the combinations of these drugs using a series of cytotoxic and apoptosis assays.
RESULTS: Tumor cells transfected with antisense p53 or p21WAF1/CIP1 exhibited a significant increase in their sensitivity to paclitaxel. The reduced protein levels of p53 and p21WAF1/CIP1 were also found to abrogate the inhibitory effects of 5-FU on paclitaxel-induced mitotic arrest and apoptosis.
CONCLUSION: These findings suggest that the status of p53 and p21WAF1/CIP1 might play an important role in tumor cell susceptibility to paclitaxel and its combination with other drugs such as 5-FU.
MATERIALS AND METHODS: In this study, human breast cancer BCap37 cells were transfected with either sense or antisense p53 or p21WAF1/CIP1. The established stable transfectants were then analyzed for an altered sensitivity to paclitaxel, 5-FU or the combinations of these drugs using a series of cytotoxic and apoptosis assays.
RESULTS: Tumor cells transfected with antisense p53 or p21WAF1/CIP1 exhibited a significant increase in their sensitivity to paclitaxel. The reduced protein levels of p53 and p21WAF1/CIP1 were also found to abrogate the inhibitory effects of 5-FU on paclitaxel-induced mitotic arrest and apoptosis.
CONCLUSION: These findings suggest that the status of p53 and p21WAF1/CIP1 might play an important role in tumor cell susceptibility to paclitaxel and its combination with other drugs such as 5-FU.