P16INK4A is required for cisplatin resistance in cervical carcinoma SiHa cells

Li,Yueran; Xiao,Songshu; Dan,Liu; Xue,Min

doi:10.3892/ol.2014.2814

March-2015 Volume 9 Issue 3

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March-2015 Volume 9 Issue 3

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Article Open Access

P16INK4A is required for cisplatin resistance in cervical carcinoma SiHa cells

Authors:
- Yueran Li
- Songshu Xiao
- Liu Dan
- Min Xue
View Affiliations / Copyright

Affiliations: Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China

Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 1104-1108
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Published online on: December 19, 2014

https://doi.org/10.3892/ol.2014.2814
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Abstract

Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer‑related mortality in females worldwide, accounting for 10‑15% of cancer-related mortalities. Cytological screening and DNA testing for high-risk human papillomavirus (HPV) types have markedly decreased the rates of cervical cancer in developed countries, however, for vulnerable populations without access to health care, cervical cancer remains a considerable problem. Chemotherapeutic agents such as cisplatin (DDP) are considered as first‑line treatment for cervical carcinoma. Although initially patients often exhibit high responsiveness, the majority eventually develop DDP resistance. However, the mechanisms underlying this process remain unclear. Furthermore, patients with metastatic cancer and those exhibiting persistent or recurrent disease after platinum‑based chemoradiotherapy have limited options and thus, non‑platinum combination chemotherapy has been proposed as a strategy to circumvent platinum resistance, however, novel therapeutic strategies are required. In the present study, P16 expression was analyzed by quantitative‑polymerase chain reaction and western blot analysis in SiHa and SiHa-DDP cells and the interaction between P16 and CDK4 was detected via co-immunoprecipitation. In addition, the proliferation and apoptosis rates of P16 knockdown SiHa-DDP cells were measured by MTT assay and Annexin V flow cytometry and the subsequent changes in cyclin D1 and pRb expression were analyzed by western blot analysis. In this study, a high level of P16INK4A expression and its enhanced interaction with cyclin‑dependent kinase‑4 in cervical carcinoma DDP‑resistance cells (SiHa‑DDP) was identified, which was associated with the inactivation of phosphorylated retinoblastoma protein (pRb). Knockdown of P16INK4A significantly induced cellular growth, when compared with the control cells, via the upregulation of pRb, and also promoted apoptosis following treatment with DDP. The results of this study indicated, for the first time, that P16INK4A is required for DDP resistance in cervical carcinoma SiHa cells and, thus, these results may lead to the development of novel strategies for the treatment of chemoresistant cervical carcinoma.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

P16INK4A is required for cisplatin resistance in cervical carcinoma SiHa cells

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