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Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo

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Abstract

A recent report showed that reversine treatment could induce murine myoblasts dedifferentiation into multipotent progenitor cells and inhibit proliferation of some tumors, and other reports showed that apoptosis of lung adenocarcinoma cells could be induced by aspirin. The aim of the present study was to evaluate the synergistic antitumor effects of reversine and aspirin on cervical cancer. The inhibition rate of reversine and aspirin on cervical cancer cell lines’ (HeLa and U14) was determined by MTT method, cell cycle of HeLa and U14 cells was analyzed by FACS, mitochondrial membrane potential of HeLa and U14 was detected using a JC-1 kit. HeLa and U14 colony formation was analyzed by soft agar colony formation assay. The expression of caspase-3, Bcl-2/Bax, cyclin D1 and p21 was detected by qRT-PCR and Western Blotting. Moreover, tumor weight and tumor volume was assessed using a murine model of cervical cancer with U14 cells subcutaneously (s.c.) administered into the neck, separately or combined with drug administration via the intraperitoneal (i.p.) route. The inhibition rate of cells in the combination group (10 μmol/L reversine, 10 mmol/L aspirin) increased significantly in comparison to that when the drugs were used alone (P < 0.05); moreover, this combination could synergistically inhibit the proliferation of five cervical cancer cell lines (HeLa, U14, Siha, Caski and C33A). In the therapeutic mouse model, tumor weight and tumor volume of cervical cancer bearing mice was more reduced when compared with the control agents (P < 0.05) in tumor-bearing mice. The combination of reversine and aspirin exerts synergistic growth inhibition and apoptosis induction on cervical cancers cells.

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Acknowledgments

This work was supported by Grant of a Research Contact with the Education Bureau of Henan Province (No.: 2011A320017).

Conflict of interest

The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Health Road, Weihui City, 453100, Henan Province, China

    Hai-xia Qin, Jun Yang, Shao-ping Li & Xiao-li Ding

  2. Department of Interventional Radiology, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Health Road, Weihui City, 453100, Henan Province, China

    Hong-kai Cui

  3. Operating Room, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Health Road, Weihui City, 453100, China

    Wei Zhang

  4. Department of Dermatovenereology, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Health Road, Weihui City, 453100, Henan Province, China

    Yong-hua Xia

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  1. Hai-xia Qin
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  2. Jun Yang
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  3. Hong-kai Cui
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  4. Shao-ping Li
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Correspondence to Yong-hua Xia.

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Qin, Hx., Yang, J., Cui, Hk. et al. Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo. Cytotechnology 65, 643–653 (2013). https://doi.org/10.1007/s10616-012-9520-8

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  • DOI: https://doi.org/10.1007/s10616-012-9520-8

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