ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>AxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.</p>
Subject(s)
Animals , Humans , Male , Mice , Adenoviridae , Genetics , Metabolism , Physiology , Adenovirus E1A Proteins , Genetics , Adenovirus E1B Proteins , Genetics , Antimetabolites, Antineoplastic , Pharmacology , Therapeutic Uses , Carcinoma, Renal Cell , Drug Therapy , Therapeutics , Cell Cycle , Genetics , Cell Line , Cell Line, Tumor , Cell Proliferation , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Deoxycytidine , Pharmacology , Therapeutic Uses , Flow Cytometry , Immunohistochemistry , Mice, Inbred BALB C , Mice, SCID , Oncolytic Virotherapy , Receptors, Virus , Genetics , Metabolism , Xenograft Model Antitumor AssaysABSTRACT
The human CD80 full-length encoding cDNA was cloned by RT-PCR, and inserted into El-substituted aden-ovirus vector pAxlcw. Subsequently, the hCD80 recombinant adenovirus vector was cotransfected into 293 cells together with EcoT22I-digested Ad5-TPC, and the replication-deficient hCD80 recombinant adenovirus was generated efficiently by homologous recombination, with the tilers of 4?10~9pfu/ml. Infected with prepared hCD80 recombinant adenovirus in vitro, Hela cells expressed high levels of hCD80 48 hours after infection. These suggest that COS/TPC is an efficient method to prepare recombinant adenoviruses and the prepared hCD80 adenovirus could be used in cancer gene therapy.
