Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells
| Autor: | Shengjun Fu, Ronald Rodriguez, Chunjie Mao, Fang Wang, Zuncheng Zhang, Zhiping Wang, Jianzhong Lu, Shuwen Li, Renju Li, Hongjuan Zhang, Zhenxing Zhai |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncolytic adenovirus Cell Survival viruses Genetic enhancement medicine.medical_treatment Gendicine Biology Adenoviridae 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Radiology Nuclear Medicine and imaging MTT assay Adenovirus infection Oncolytic Virotherapy Recombination Genetic Bladder cancer Radiological and Ultrasound Technology medicine.disease Molecular biology Combined Modality Therapy Prostate Stem Cell Antigen Radiation therapy Oncolytic Viruses 030104 developmental biology Treatment Outcome Urinary Bladder Neoplasms 030220 oncology & carcinogenesis Radiotherapy Conformal |
| Zdroj: | International journal of radiation biology. 93(2) |
| ISSN: | 1362-3095 |
| Popis: | 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.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.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.Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer. |
| Databáze: | OpenAIRE |
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