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Original Research

Open Access

Mifepristone sensitizing cisplatin for cervical adenocarcinoma HeLa cell sensitivity to chemotherapy and its mechanism

  • Caihong Li1
  • Hong Ye1,*,

1Department of Gynecology and Obstetrics, First Clinical Medical Science College of China Three Gorges University, Yichang (China)

DOI: 10.12892/ejgo340207 Vol.34,Issue 2,March 2013 pp.142-147

Published: 24 March 2013

*Corresponding Author(s): Hong Ye E-mail: yehong998@126.com

Abstract

Objective: The study was designed to investigate proliferation inhibition for cervical adenocarcinoma HeLa cell treated with cisplatin combined with mifepristone and access its possible mechanism. Materials and Methods: HeLa cell was processed by different concentrations of mifepristone, cisplatin, and their combination respectively. Cell’s proliferation inhibition rate and induction apoptosis ability were detected by MTT assay, FCM; the expression of P53, survivin and HPV E6 protein were measured by Western Blot. Results: The results showed that cisplatin inhibits proliferation of HeLa cells in different concentrations (p < 0.01). Mifepristone had no effect on HeLa cell proliferation inhibition rate during 24 and 48 hours (p > 0.05). Mifepristone at low concentrations (≤ 10 μmol/l) combined with cisplatin can significantly enhance the inhibitory effect of cisplatin on HeLa cell line. Flow cytometry showed that mifepristone at low concentrations (≤ 10 μmol/l) combined with cisplatin can induce apparent apoptosis of HeLa cell line in concentration dependent manner. Western blotting demonstrated that the expression of P53 protein increased and the expression of HPV E6 survivin protein decreased in HeLa cells treated with MIF at low concentrations (≤ 10 μmol/l) combined with cisplatin. Conclusion: Mifepristone at low concentrations (≤ 10 μmol/l) can enhance chemosensitivity and capability of inducing apoptosis of cisplatin to HeLa cells. The strengthening effect of growth inhibition and chemosensitivity to cisplatin of mifepristone are associated with down-regulating HPV E6 survivin protein and upregulating p53 protein.

Keywords

Mifepristone; Cervical cancer; Cisplatin; Chemotherapy sensitivity.

Cite and Share

Caihong Li,Hong Ye. Mifepristone sensitizing cisplatin for cervical adenocarcinoma HeLa cell sensitivity to chemotherapy and its mechanism. European Journal of Gynaecological Oncology. 2013. 34(2);142-147.

References

[1] Sherman M.E., Wang S.S., Carreon J., Devesa S.S.: “Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival”. Cancer, 2005, 103, 1258.

[2] Jinghe L., Xiaoman D.: “Current clinical diagnosis and treatment in gynecological oncology”. Oncol. Progress, 2006, 4, 2.

[3] Cruet-Hennequart S., Glynn M.T., Murillo S.L., Coyne S., Carty M.P.: “Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin”. DNA Repair, 2008, 7, 582.

[4] Jianli H., Shiying Y., Xianglin Y., Huihua X., Jinxiang Y., Guoqing H.: “Cisplatin modulates the expression of microvessel density and apoptosis in radiotherapy of cervical cancer”. Cancer Res. Prev. Treat., 2004, 31, 81.

[5] Koivisto-Korander R., Leminen A., Heikinheimo O.: “Mife pri - stone as treatment of recurrent progesterone receptor-positive uterine leiomyosarcoma”. Obstet. Gynecol., 2007, 109, 512.

[6] Lee D., Kwon J.H., Kim E.H., Kim E.S., Choi K.Y.: “HMGB2 stabilizes p53 by interfering with E6/E6AP-mediated p53 degradation in human papillomavirus-positive HeLa cells”. Cancer Letters, 2010, 292, 125.

[7] Halevy A., Samuk I., Halpern Z., Copel L., Sandbank J., Ziv Y.: “Mifepristone (RU486), a pure antiprogesterone drug, in combination with vinblastine for the treatment of progesterone receptor desmoid tumor”. Tech. Coloproctol., 2010, 14, 265.

[8] Saha P., Hödl C., Strauss W.S.L., Steiner R., Goessler W., Jumert O. et al.: “Synthesis, in vitro progesterone receptors affinity of gadolinium containing mifepristone conjugates and estimation of binding sites in human breast cancer cells”. Bioorg. Med. Chem., 2010, 18, 1891.

[9] Schaff E.A.: “Mifepristone: ten years later”. Contraception, 2010, 81, 1.

[10] Yang Y.C., Hsu Y.T., Wu C.C., Chen H.T., Chang M.S.: “Silencing of astrin induces the p53-dependent apoptosis by suppression of HPV18 E6 expression and sensitizes cells to paclitaxel treatment in HeLa cells”. Biochem. Biophys. Res. Commun., 2006, 343, 428.

[11] Bratholomew J.S., Glenville S., Sarkar S., Burt D.J., Stanley M.A., Ruiz-Cabello F. et al.: “Integration of high-risk human papillomavirus DNA is linked to the down-regulation of class I human leukocyte antigens by steroid hormones in ceavical tumor cells”. Cancer Res., 1997, 57, 937.

[12] Breadsmore D.M., Verbeck C.S., Davies C.L., Guillou P.J., Clark G.W.: “Apoptotic and proliferative indexes in esophageal cancer: predictors of response to neoadjuvant therapy apoptosis and proliferation in esophageal cancer”. J. Gastrointest. Surg., 2003, 7, 77.

[13] Temme A., Rodriguez J.A., Hendruschk S., Günes S., Wigle B., Schäkel K. et al.: “Nuclear localization of Survivin renders HeLa tumor cells more sensitive to apoptosis by induction of p53 and Bax”. Cancer Lett., 2007, 250, 177.

[14] Branca M., Giorgi M., Santini D., Di Bonito L., Ciotti M., Costa S. et al.: “Survivin as a marker of cervical intraepithelial neoplasia and high-risk human papillomavirus and a predictor of virus clearance and prognosis in cervical cancer”. Am. J. Clin. Pathol., 2005, 124, 113.

[15] Reddy V.G., Khanna N., Singh N., Vitamin C.: “Augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing p53”. Biochem. Biophys. Res. Commun., 2001, 282, 409.

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