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International Journal of Molecular Medicine
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June-2014 Volume 33 Issue 6

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

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Article

Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells

  • Authors:
    • Chu-Yue Zhang
    • Wei Bao
    • Li-Hua Wang
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China
  • Pages: 1577-1585
    |
    Published online on: April 7, 2014
       https://doi.org/10.3892/ijmm.2014.1731
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Abstract

Studies have suggested that p16ink4a may be a surrogate biomarker for the diagnosis of cervical cancer; however, the function of p16ink4a in human cervical cancer cells remains largely unknown. Therefore, in this study, we aimed to investi­gate the role of p16ink4a in human cervical cancer cells. Immunocytochemistry was used to examine invasive squamous cell carcinoma and its precancerous lesions. p16ink4a-siRNA was transfected into SiHa and HeLa cells to deplete its expression. The cellular levels of p16ink4a mRNA and protein were detected by qRT-PCR and western blot analysis. Proliferation rates were assessed by methyl thiazolyl tetrazolium (MTT) and plate colony formation assays. Cellular migration and invasion ability were assessed by a wound healing assay and Transwell assay. Cellular apoptosis and the cell cycle were measured by flow cytometry. The protein levels of retinoblastoma (Rb), phosphorylated Rb (phospho-Rb), cyclin D1 and caspase-3 were determined by western blot analysis. The results revealed that p16ink4a was overexpressed in the cervical cancer and precancerous lesions (P<0.05). The downregulation of p16ink4a in the SiHa and HeLa cells inhibited their proliferation, migration and invasion. In the SiHa cells, p16ink4a-siRNA also induced G1 cell cycle arrest and apoptosis. Western blot analysis revealed that the downregulation of p16ink4a in the SiHa cells markedly induced caspase-3 activation and decreased cyclin D1 expression. These data suggest that the overexpression of p16ink4a appears to be useful in monitoring cervical precancerous lesions, which supports that the hypothesis that p16ink4a is a surrogate biomarker for the diagnosis of cervical cancer. The therapeutic targeting of overexpressed p16ink4a in the p16ink4a-cyclin-Rb pathway may be a useful strategy in the treatment of cervical cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang C, Bao W and Wang L: Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells. Int J Mol Med 33: 1577-1585, 2014.
APA
Zhang, C., Bao, W., & Wang, L. (2014). Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells. International Journal of Molecular Medicine, 33, 1577-1585. https://doi.org/10.3892/ijmm.2014.1731
MLA
Zhang, C., Bao, W., Wang, L."Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells". International Journal of Molecular Medicine 33.6 (2014): 1577-1585.
Chicago
Zhang, C., Bao, W., Wang, L."Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells". International Journal of Molecular Medicine 33, no. 6 (2014): 1577-1585. https://doi.org/10.3892/ijmm.2014.1731
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang C, Bao W and Wang L: Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells. Int J Mol Med 33: 1577-1585, 2014.
APA
Zhang, C., Bao, W., & Wang, L. (2014). Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells. International Journal of Molecular Medicine, 33, 1577-1585. https://doi.org/10.3892/ijmm.2014.1731
MLA
Zhang, C., Bao, W., Wang, L."Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells". International Journal of Molecular Medicine 33.6 (2014): 1577-1585.
Chicago
Zhang, C., Bao, W., Wang, L."Downregulation of p16ink4a inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells". International Journal of Molecular Medicine 33, no. 6 (2014): 1577-1585. https://doi.org/10.3892/ijmm.2014.1731
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