E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma.
- Author:
Hua WANG
1
;
Makoto SATOH
;
Gui-Ping CHEN
;
De-Chuan LI
;
Hirofumi HAMADA
;
Yoichi ARAI
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; metabolism; physiology; Adenovirus E1A Proteins; genetics; Adenovirus E1B Proteins; genetics; Animals; Antimetabolites, Antineoplastic; pharmacology; therapeutic use; Carcinoma, Renal Cell; drug therapy; therapy; Cell Cycle; drug effects; genetics; Cell Line; Cell Line, Tumor; Cell Proliferation; drug effects; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Deoxycytidine; analogs & derivatives; pharmacology; therapeutic use; Flow Cytometry; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, SCID; Oncolytic Virotherapy; Receptors, Virus; genetics; metabolism; Xenograft Model Antitumor Assays
- From: Chinese Medical Journal 2011;124(7):1082-1087
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDOur 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.
METHODSCytopathic 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.
RESULTSAxdAdB-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.
CONCLUSIONAxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.
