Synergistic effect of bladder cancer-specific oncolytic adenovirus in combination with chemotherapy.
Synergistic effect of bladder cancer-specific oncolytic adenovirus in combination with chemotherapy.
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膀胱癌特异性溶瘤腺病毒联合化疗的协同作用
DOI：
10.3892/ol.2017.6416
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发表时间：
2017-08
期刊：
影响因子：
2.9
通讯作者：
Rodriguez R
中科院分区：
文献类型：
--
作者：
Li S;Wang F;Zhai Z;Fu S;Lu J;Zhang H;Guo H;Hu X;Li R;Wang Z;Rodriguez R
腺病毒E1 A基因治疗可增强肿瘤细胞对化疗诱导的细胞死亡的敏感性。我们先前的研究开发了一种具有尿斑蛋白II（UPII）启动子控制E1 A表达的尿路上皮特异性溶瘤血清型5腺病毒（Ad 5）。本研究探讨了这种尿路上皮特异性重组腺病毒（Ad 5-UPII-E1 A）是否增强丝裂霉素（MMC）和羟基喜树碱（HCPT）的增敏作用和药物诱导的膀胱癌细胞凋亡。MTT试验的结果表明，联合治疗，使用Ad 5-UPII-E1 A和MMC或HCPT，协同抑制膀胱癌细胞的活力，在剂量和时间依赖性的方式相比，任何一个单独的代理。当单独用Ad 5-UPII-E1 A处理细胞时，它们停滞在G1期，但是通过流式细胞术的细胞周期分析显示，当用联合治疗处理时，细胞周期停滞在S期。MMC或HCPT处理增强Ad 5-UPII-E1 A诱导的5，637细胞凋亡，通过透射电子显微镜观察。Western blot结果显示MMC和HCPT均能促进Ad 5-UPII-E1 A表达，且呈剂量依赖性。本研究表明，Ad 5-UPII-E1 A与MMC或HCPT联合使用在涉及促进膀胱癌细胞系凋亡的过程中产生协同细胞毒性。MMC和HCPT也能促进Ad 5-UPII-E1 A的溶瘤作用。因此，使用Ad 5-UPII-E1 A联合MMC或HCPT的治疗可能是膀胱癌对化疗敏感的有吸引力的策略。
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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影响因子：
21.3
作者：
Duelli, DM;Lazebnik, YA
通讯作者：
Lazebnik, YA
影响因子：
6.4
作者：
Alonso, M. M.;Gomez-Manzano, C.;Fueyo, J.
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影响因子：
4.2
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作者：
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通讯作者：
Zhou L
影响因子：
10.5
作者：
de Stanchina, E;McCurrach, ME;Lowe, SW
通讯作者：
Lowe, SW