Synergistic effect of bladder cancer-specific oncolytic adenovirus in combination with chemotherapy

Shuwen Li, Fang Wang, Zhenxing Zhai, Shengjun Fu, Jianzhong Lu, Hongjuan Zhang, Hongyu Guo, Xuemei Hu, Renju Li, Zhiping Wang, Ronald Rodriguez

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Gene therapy with adenoviral early region gene (E1A) may enhance the susceptibility of neoplastic cells to chemotherapy-induced cell death. Our previous study developed a urothelium-specific oncolytic serotype 5 adenovirus (Ad5) with the uroplakin II (UPII) promoter controlling E1A expression. The present study investigated whether this urothelium-specific recombinant adenovirus (Ad5-UPII-E1A) enhanced mitomycin (MMC) and hydroxycamptothecin (HCPT) sensitization and drug-induced apoptosis in bladder cancer cells. The results of the MTT assay revealed that combination therapy, using Ad5-UPII-E1A and MMC or HCPT, synergistically inhibited the viability of bladder cancer cells in a dose-and time-dependent manner when compared with either agent alone. When cells were treated with Ad5-UPII-E1A alone they arrested in the G1 phase, but cell cycle analysis by flow cytometry revealed S phase arrest when treated with combined therapy. Treatment with MMC or HCPT enhanced Ad5-UPII-E1A-induced apoptosis in 5,637 cells, observed by transmission electron microscopy. Western blot analysis revealed that MMC and HCPT enhanced the E1A expression of the Ad5-UPII-E1A vectorin a dose-dependent manner. The present study demonstrated that Ad5-UPII-E1A combined with MMC or HCPT resulted in synergistic cytotoxicity in a process which involved the promotion of apoptosis in bladder cancer cell lines. MMC and HCPT also promoted the oncolytic effect of Ad5-UPII-E1A. Thus, treatment using Ad5-UPII-E1A combined with MMC or HCPT may be an attractive strategy for the sensitization of bladder cancer to chemotherapy.

Original languageEnglish (US)
Pages (from-to)2081-2088
Number of pages8
JournalOncology Letters
Volume14
Issue number2
DOIs
StatePublished - 2017

Keywords

  • Chemotherapy
  • Hydroxycamptothecin
  • Mitomycin
  • Oncolytic adenovirus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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