TY - JOUR
T1 - Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells
AU - Zhang, Hongjuan
AU - Wang, Fang
AU - Mao, Chunjie
AU - Zhang, Zuncheng
AU - Fu, Shengjun
AU - Lu, Jianzhong
AU - Zhai, Zhenxing
AU - Li, Renju
AU - Li, Shuwen
AU - Rodriguez, Ron
AU - Wang, Zhiping
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Purpose: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. Materials and methods: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. Results: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. Conclusions: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.
AB - Purpose: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. Materials and methods: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. Results: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. Conclusions: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.
KW - Bladder cancer
KW - gene therapy
KW - oncolytic adenovirus
KW - radiation therapy
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U2 - 10.1080/09553002.2017.1231942
DO - 10.1080/09553002.2017.1231942
M3 - Article
C2 - 27600610
AN - SCOPUS:84991037434
SN - 0955-3002
VL - 93
SP - 174
EP - 183
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 2
ER -