Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK

• Published in: Oncology research 2015-09, Vol.22 (4), p.225-233
• Main Authors: Wang, Hong-yong, Liu, Zhong-shan, Qiu, Ling, Guo, Jie, Li, Yun-feng, Zhang, Jun, Wang, Tie-jun, Liu, Xiao-dong
• Format: Article
• Language: English
• Subjects: Apoptosis - radiation effects; Cell Proliferation - radiation effects; Cell Survival - radiation effects; Cervical Cancer; Down-Regulation; Enzyme Activation; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HeLa Cells; Humans; P38 Mapk; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Protein Phosphatase 2C; Radiation Tolerance; RNA Interference; Sb203580; Signal Transduction - radiation effects; Time Factors; Transfection; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - radiotherapy; Wild-type p53-induced phosphatase (Wip1); Γ-Irradiation
• ISSN: 0965-0407; 1555-3906
• DOI: 10.3727/096504015X14386062091479

The objectives of the study were to investigate the functional role and potential mechanism of wild-type p53-induced phosphatase (Wip1) in cervical cancer cell line HeLa cells, along with the effect of knockdown of Wip1 in combination with γ-irradiation on the HeLa cells. Expression of Wip1 was silenced or overexpressed. After transfection, cell viability was determined. Moreover, γ-irradiation and SB203580 were performed to explore the effect of colony formation and cell apoptosis. Likewise, protein expression levels of p38, p-p38, p53, and p-p53 were assessed in the presence or not of SB203580 and overexpression of Wip1. Both the mRNA and protein levels of Wip1 were significantly decreased by transfection with Wip1-specific small interfering RNA (siRNA) but were significantly increased by transfection with pcDNA3.1-Wip1. Knockdown of Wip1 significantly decreased cell growth and colony formation ability and increased apoptotic rate. Additionally, better results were obtained by knockdown of Wip1 in combination with γ-irradiation. The protein expression levels of p-p38 (p