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Combination of bladder cancer-specific oncolytic adenovirus gene therapy with cisplatin on bladder cancer in vitro

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Tumor Biology

Abstract

Bladder cancer-specific oncolytic adenovirus Ad/PSCAE/UPII/E1A, carrying E1A gene regulated by human Uroplakin II (UPII) promoter and prostate stem cell antigen enhancer (PSCAE), could kill bladder tumor cells preferentially. The aim of this study was to examine the effects of Ad/PSCAE/UPII/E1A combined with cisplatin on human bladder cancer cells and to identify the underlying mechanisms. The combined effects of Ad/PSCAE/UPII/E1A and cisplatin on EJ, 5637, and BIU-87 bladder cancer cells were evaluated by MTT cell proliferation assay. Cell apoptosis was detected by flow cytometry with fluorescein isothiocyanate-conjugated annexin V (annexin V-FITC) and propidium iodide staining. The activation of the caspase pathway and the expression of Bcl-2 family proteins were determined by western blot assay. Ad/PSCAE/UPII/E1A adenovirus vector could infect bladder cancer cell lines selectively and induce growth inhibition effectively. Of note, the combination treatment of cisplatin and Ad/PSCAE/UPII/E1A could inhibit the proliferation of bladder cancer cells significantly compared with the “alone” treatment. Furthermore, Ad/PSCAE/UPII/E1A plus cisplatin combined treatment resulted in enhanced apoptosis in bladder cancer cells. The enhanced antitumor effects in vitro elicited by Ad/PSCAE/UPII/E1A plus cisplatin were closely related to the increased Fas expression and cleavage of caspase-8 and Bid and decrease in the ratio of anti- to pro-apoptotic proteins followed by activation of caspase-9 and caspase-3, which may contribute to the activation of extrinsic and intrinsic apoptotic pathways. Our results indicate that the combination of Ad/PSCAE/UPII/E1A with cisplatin exerts a synergistic antitumor effect on human bladder cancer cells and is a potential combined treatment strategy for bladder cancer.

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Acknowledgments

This work was supported by the National High-tech R&D Program of China (863 Program) (Grant No. 2008AA02Z421) and National Natural Science Foundation of China (Grant No. 30772177/H1619).

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Authors and Affiliations

  1. School of Life Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China

    Li Wang

  2. Department of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Cuiyingmen No. 82, Linxia Road, Lanzhou, 730030, Gansu, China

    Li Wang, Yunxin Zhang, Jinxia Zhao, Erlong Xiao, Jianzhong Lu, Shengjun Fu & Zhiping Wang

  3. Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China

    Li Wang

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  1. Li Wang
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  2. Yunxin Zhang
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  3. Jinxia Zhao
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Correspondence to Zhiping Wang.

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Li Wang and Yunxin Zhang contributed equally to this work and are joint first authors.

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Wang, L., Zhang, Y., Zhao, J. et al. Combination of bladder cancer-specific oncolytic adenovirus gene therapy with cisplatin on bladder cancer in vitro. Tumor Biol. 35, 10879–10890 (2014). https://doi.org/10.1007/s13277-014-2353-7

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  • DOI: https://doi.org/10.1007/s13277-014-2353-7

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