Wild Type p53 Inhibits Apoptosis Induced by bcl2 Silencing in Malignant Tumor Cells

Abstract

Abstract In cancer gene therapy, anti-apoptotic gene bcl2 was one of the target to be aimed in some malignant tumor cells. Theoretically, when bcl2 expression is suppressed by siRNA technique, malignant tumor cells would undergo more apoptosis. However, in our study, different malignant tumor cells responded differently as human non-small cell carcinoma cell A549 was sensitive while cervical carcinoma cell Hela was resistant to bcl2 silencing. To investigate if tumor suppressor p53, which is wild typed in A549 but functionally mutant in Hela, plays a role in the different response to bcl2 silencing in these two cell lines, p53 inhibitor pifithrin-µ was applied to explore p53’s impact on apoptosis initiated by bcl2 knockdown. Results showed that p53 involved in the upregulation of transcription regulator nuclear factor-κB (NFκB) phosphorylated at Ser536 which could enhance apoptosis promoting gene bax expression to induce p53-proficient cell apoptosis.