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

Hua Wang, Makoto Satoh, Gui Ping Chen, De Chuan Li, Hirofumi Hamada, Yoichi Arai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1082-1087
Number of pages6
JournalChinese Medical Journal
Volume124
Issue number7
DOIs
Publication statusPublished - 2011 Apr 5

Keywords

  • Adenovirus
  • Gemcitabine
  • Oncolysis
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Medicine(all)

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