Article Abstract

P53 introduction enhances chemotherapy-induced apoptosis in Hela cells

Authors: Wei Sun, Xiangxuan Zhao, Zaiming Lu, Qiyong Guo

Abstract

Background: Cervical cancer remains a global health-related issue with over half a million new cases reported annually. However, despite different therapeutic regimens being utilized, over a million women die of cervical cancer each year. This makes it the most lethal cancer and indicates the urgent need for novel therapeutic strategies. This study was to investigate the functional roles of p53 over-expression in enhancing Lobaplatin (loba)-induced cell growth inhibition and apoptosis in cervical carcinoma cells.
Methods: Hela cells were treated with recombinant p53 adenovirus (rAdp53), lobaplatin (loba), or rAdp53 plus loba combination. Subsequently, morphology, Hoechst staining, flow cytometry, and cell proliferation assay were conducted to measure apoptosis and cell growth inhibition in vitro. Western blotting was performed to assess protein expression. Xenograft tumor mouse model was used to detect the combined anti-cancer effects of rAdp53 and loba in vivo.
Results: In vitro assays demonstrated that neither sub-lethal rAdp53 nor loba have any apparent apoptotic effect on Hela cells. The combination of rAdp53 and loba induced significant apoptosis and cell growth inhibition. P53 over-expression up-regulated the proapoptotic proteins Bax and Bak. Xenograft cervical tumors derived from Hela cells demonstrated that co-treatment with rAdp53 and loba effectively inhibited tumor growth in vivo.
Conclusions: P53 restoration can sensitize cervical cancer cells to loba to induce apoptosis and cell growth inhibition.