Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death.
Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death.
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DOI：
10.3892/mmr.2014.2987
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发表时间：
2015-03
影响因子：
3.4
通讯作者：
Ren-fu Chen;Yueyan Li;Liantao Li;Qian Cheng;G. Jiang;Junnian Zheng
中科院分区：
文献类型：
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作者：
Ren-fu Chen;Yueyan Li;Liantao Li;Qian Cheng;G. Jiang;Junnian Zheng
肾癌是最常见的肾脏恶性肿瘤，有转移性疾病的患者预后较差。细胞凋亡抑制和显著侵袭性是肾癌的显著特征。本研究利用Ki67启动子取代E1a基因的天然病毒启动子，构建了表达IL-24基因的双调控溶瘤腺病毒(Ki67-ZD55-IL-24)。目的：探讨Ki67-ZD55-IL-24基因治疗与放射治疗联合应用是否通过线粒体凋亡增加对肾癌细胞的细胞毒作用。这些数据表明，这一新策略有可能进一步发展成为治疗肾癌的有效方法。结果表明，与其他药物相比，Ki67-ZD55-IL-24联合放射治疗可通过增加对黑色素瘤细胞的诱导凋亡而显著增强抗肿瘤活性。
Renal cell carcinoma is the most frequent kidney malignancy and patients with metastatic disease have a poor prognosis. Suppressed apoptosis and marked invasiveness are distinctive features of renal cell carcinoma. In the present study, a dual‑regulated oncolytic adenovirus expressing the interluekin (IL)‑24 gene (Ki67‑ZD55‑IL‑24) was constructed utilizing the Ki67 promoter to replace the native viral promoter of the E1A gene. Whether the combination of Ki67‑ZD55‑IL‑24‑mediated gene virotherapy and radiotherapy produced increased cytotoxicity in renal cell carcinoma cells via mitochondrial apoptotic cell death was investigated. The data indicated that this novel strategy has the potential to be further developed into an effective approach to treat renal cell carcinoma. The results showed that the combination of Ki67‑ZD55‑IL‑24 and radiotherapy significantly enhanced anti‑tumour activity via increasing the induction of apoptosis in melanoma cells compared with the other agents.