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

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

doi:10.3892/ol.2017.6416

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

Authors:
- Shuwen Li
- Fang Wang
- Zhenxing Zhai
- Shengjun Fu
- Jianzhong Lu
- Hongjuan Zhang
- Hongyu Guo
- Xuemei Hu
- Renju Li
- Zhiping Wang
- Ronald Rodriguez
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Affiliations: Urologic Clinical Center of Gansu Province, Key Laboratory of Gansu Province, Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Medical Experiment Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Published online on: June 19, 2017 https://doi.org/10.3892/ol.2017.6416
Pages: 2081-2088
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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