Fiber-modified adenovirus-mediated suicide gene therapy can efficiently eliminate bladder cancer cells in vitro and in vivo
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De-Gui Wang1, Mei-Jun Zhao1, Yong-Qiang Liu1, Xiang-Wen Liu1, Hai-Tao Niu3, Yan-Feng Song1, Ying-Xia Tian1,2
1Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
2Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou 730050, China
3Department of Urology, Affiliated Hospital of Qingdao University, Qingdao 266071, China
Ying-Xia Tian, email: [email protected]
Hai-Tao Niu, email: [email protected]
Yan-Feng Song, email: [email protected]
Keywords: gene therapy, bladder cancer, suicide gene, adenovirus
Received: June 14, 2016 Accepted: September 21, 2016 Published: September 28, 2016
Adenovirus-mediated gene therapy is a promising strategy for bladder cancer treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in bladder cancer cells decreases the infection efficiency of the therapeutic adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is driven by a human UPII promoter. Then, we tested the bladder cancer specificity of the UPII promotor and the expression of the HSV-TK protein. Additionally, we observed a potent cytotoxic effects of RGDAd-UPII-TK and ganciclovir (GCV) on bladder cancer as demonstrated by reduced cell survival and morphology changes in vitro. Furthermore, we confirmed that RGDAd-UPII-TK in combination with a GCV injection could significantly reduce the established T24 tumor growth and increase apoptosis in vivo. Altogether, our results indicated that the recombinant adenovirus RGDAd-UPII-TK could target bladder cancer through valid gene therapy.
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