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Open Access Highly Accessed Research

Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells

Hai-Bin Zhu2, Kai Yang1, Yan-Qi Xie1, Yi-Wei Lin1, Qi-Qi Mao1 and Li-Ping Xie1*

  • * Corresponding author: Li-Ping Xie lpxie@yahoo.cn

  • † Equal contributors

Author Affiliations

1 Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang Province, 310003, China

2 Department of Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang Province, 310003, China

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World Journal of Surgical Oncology 2013, 11:22  doi:10.1186/1477-7819-11-22

Published: 28 January 2013

Abstract

Background

p53 is the most frequently mutated tumor-suppressor gene in human cancers. It has been reported that mutations in p53 result not only in the loss of its ability as a tumor suppressor, but also in the gain of novel cancer-related functions that contribute to oncogenesis. The present study evaluated the potential of silencing of mutant p53 by small interfering RNA in the treatment of bladder cancer cells in vitro.

Methods

We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability and flow cytometry to detect cell cycle alterations and apoptosis. The related molecular mechanisms were assessed by western blotting. We also used the MTT assay and flow cytometry to investigate if silencing of mutant p53 by knockdown with small interfering (si)RNA would change the sensitivity to cisplatin treatment.

Results

Using 5637 and T24 human bladder cancer cell lines characterized by mutations in p53, we found that silencing of the mutant p53 by RNA interference induced evident inhibition of cell proliferation and viability, which was related to the induction of G2 phase cell cycle arrest and apoptosis. Moreover, our study also showed that the p53-targeting siRNA cooperated with cisplatin in the inhibition of bladder cancer cells.

Conclusions

These findings suggest that RNA interference targeting mutant p53 may be a promising therapeutic strategy for the treatment of bladder cancer.

Keywords:
Mutant p53; RNA interference; Bladder cancer; Cisplatin; Apoptosis