Fiber-modified adenovirus-mediated suicide gene therapy can efficiently eliminate bladder cancer cells in vitro and in vivo.
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.
Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
De-Gui
DG
Wang
Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Mei-Jun
MJ
Zhao
Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Yong-Qiang
YQ
Liu
Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Xiang-Wen
XW
Liu
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao 266071, China.
Hai-Tao
HT
Niu
Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Yan-Feng
YF
Song
Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.|Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou 730050, China.
Ying-Xia
YX
Tian
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D045744:Cell Line, Tumor; D015774:Ganciclovir / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D009842:Oligopeptides; D013937:Thymidine Kinase / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*; D060170:Uroplakin II / Q000235:genetics
D009842:Oligopeptides; C554658:UPK2 protein, human; D060170:Uroplakin II; C047981:arginyl-glycyl-aspartic acid; D013937:Thymidine Kinase; D015774:Ganciclovir
adenovirus; bladder cancer; gene therapy; suicide gene
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