Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells.

摘要: Prostaglandin A2 (PGA2) suppresses tumor growth in vivo, is potently antiproliferative vitro, and a model drug for the study of mammalian stress response. Our previous studies using breast carcinoma MCF-7 cells suggested that p21(Waf1/Cip1) induction enabled to survive PGA2 exposure. Indeed, marked sensitivity human colorectal RKO cytotoxicity known be associated with lack PGA2-mediated increase expression, inhibition cyclin-dependent kinase activity, arrest. To determine if cell death following exposure could prevented by forcing expression cells, we utilized an adenoviral vector-based system. We demonstrate ectopic largely rescued from PGA2-induced apoptotic death, directly implicating as determinant cellular outcome (survival versus death) PGA2. discern whether p21(Waf1/Cip1)-mediated protection operates through implementation arrest, other growth-inhibitory treatments were studied ability attenuate death. Neither serum depletion nor suramin (a factor receptor antagonist) protected against cytotoxicity, neither induced expression. Mimosine, however, enhanced completely inhibited proliferation, exerted subsequent challenge. Taken together, our results protective role during provide strong evidence arrest contributes this influence.