Overexpression of p21waf1 Leads to Increased Inhibition of E2F-1 Phosphorylation and Sensitivity to Anticancer Drugs in Retinoblastoma-negative Human Sarcoma Cells

摘要: The effect of overexpression p21waf1 on drug sensitivity was studied in an osteosarcoma cell line (SaOs-2) lacking both p53 and functional retinoblastoma protein using a tetracycline (TC)-inducible expression system. barely detectable SaOS-2 cells incubated the presence TC. After TC withdrawal, high levels were induced these cells. These p21waf1-induced showed increased to doxorubicin, tomudex, methotrexate as compared uninduced cells; this condition is associated with apoptosis. Expression reduced cyclin A-associated kinase activity and, surprisingly, resulted inhibition phosphorylation E2F-1 binding activity. An S-G2 cycle arrest/delay increase E2F-responsive genes ( dihydrofolate reductase thymidylate synthase ) correspondingly observed. Overexpression may mediate anticancer drugs by inhibiting phosphorylation, which contribute delay susceptibility