E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma

Wang Hua ¹ ^* Makoto Satoh ² Chen Guiping ¹ Li Dechuan ¹ Hirofumi Hamada ³ Yoichi Arai ⁴

文摘	Background Our previous studies have demonstrated potent oncolysis efficacy of the E1A, E1B double-restricted replication-competent oncolytic adenovirus AxdAdB-3 for treatment of bladder cancer. Here, we reported the feasibility and efficacy of AxdAdB-3 alone, or in combination with gemcitabine for treating renal cell carcinoma. Methods Cytopathic effects of AxdAdB-3 were evaluated in human renal cell carcinoma cell lines TOS-1, TOS-2, TOS-3, TOS-3LN, SMKT-R3, SMKT-R4 and ACHN, and in normal human renal proximal tubule epithelial cells (RPTEC). AxdAdB-3 induced down-regulation of the cell cycle was determined by flow cytometry. Combination therapies of AxdAdB-3 with gemcitabine were evaluated in vitro and in vivo on subcutaneous TOS-3LN tumors in a severe combined immunodeficiency disease (SCID) mouse model. Results AxdAdB-3 was potently cytopathic against the tested most renal cell carcinoma cell lines including TOS-2, TOS-3, TOS-3LN, SMKT-R3 and SMKT-R4, while normal human RPTEC were not destroyed. AxdAdB-3 effectively induced cell cycle S-phase entry. Combined therapy of AxdAdB-3 with gemcitabine demonstrated stronger antitumor effects in vitro and in vivo compared with either AxdAdB-3 or gemcitabine alone. Conclusion AxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.
来源	Chinese Medical Journal ,2011,124(7):1082-1087 【核心库】
DOI	10.3760/cma.j.issn.0366-6999.2011.07.024
关键词	oncolysis ; adenovirus ; gemcitabine ; renal cell carcinoma
地址	1. Department of Urology, Zhejiang Cancer Hospital, Zhejiang, Hangzhou, 310022 2. Department of Urology, Se-en Hospital, Japan, Japan, Tagajyo 3. Department of Molecular Medicine, Sapporo Medical University, Japan, Japan, Sapporo 4. Division of Urology, Chair of Surgery Tohoku University Graduate School of Medicine, Japan, Japan, Sendai
语种	英文
文献类型	研究性论文
ISSN	0366-6999
学科	外科学
基金	in part by the Qianjiang Program of Zhejiang Province
文献收藏号	CSCD:4428515