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Combination treatment with dihydrotanshinone I and irradiation enhances apoptotic effects in human cervical cancer by HPV E6 down-regulation and caspases activation

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Abstract

The aim of this study was to investigate the effect of dihydrotanshinone I (DI) in inhibiting the growth of human cervical cancer cells both in vitro and in vivo, and molecular targets in HeLa cells when treated by DI or irradiation with or without being combined. In this study, MTT, clonogenic assay, flow cytometry, and Western blotting were performed to assess the effect of treatment on cells. After treatment with IR, DI, and DI + IR, the apoptosis was 5.8, 13.3 and 22.5% (P < 0.05 vs. control), respectively. Clonogenic assay revealed that the survival of irradiated HeLa cell was significantly reduced by DI treatment. Combination treatment with IR and DI could down-regulate HPV E6 gene expression. Effect of DI on up-regulation of p21 expression and down-regulation of cyclin B1, p34cdc2 expression in irradiated HeLa cell was concomitant with cell cycle arrest in G2 phase. The significant increase in caspase-3 activity was also observed in the combination treatment. When HeLa cells were grown as xenografts in nude mice, combination treatment with DI and IR induced a significant decrease in tumor growth, and without signs of general or organ toxicity. These data suggest DI should be tested as the radiosensitizer in vitro and in vivo, which has potential in the treatment of human cervical cancer.

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Acknowledgments

Thanks to Prof. Chen Wang for providing advice and her technical assistance, and all members of the laboratory for insightful suggestions. This research was supported by grants from the key project of Tianjin science and technology support (2010KZ75).

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Authors and Affiliations

  1. Department of Pharmacy, Breast Cancer Prevention Key Laboratory of Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060, China

    Yintao Ye, Yajing Li & Chen Wang

  2. The Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, 300192, China

    Wenqing Xu

  3. GlaxoSmithKline, Tianjin Smith Kline & French Laboratories Ltd, Tianjin, 300163, China

    Wei Zhong

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  1. Yintao Ye
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Correspondence to Chen Wang.

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Ye, Y., Xu, W., Zhong, W. et al. Combination treatment with dihydrotanshinone I and irradiation enhances apoptotic effects in human cervical cancer by HPV E6 down-regulation and caspases activation. Mol Cell Biochem 363, 191–202 (2012). https://doi.org/10.1007/s11010-011-1171-0

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