Combined therapy of oncolytic adenovirus and temozolomide enhances lung cancer virotherapy in vitro and in vivo.
Combined therapy of oncolytic adenovirus and temozolomide enhances lung cancer virotherapy in vitro and in vivo.
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DOI：
10.1016/j.virol.2015.10.019
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发表时间：
2016-01
期刊：
影响因子：
3.7
通讯作者：
McMasters KM
中科院分区：
文献类型：
--
作者：
Gomez-Gutierrez JG;Nitz J;Sharma R;Wechman SL;Riedinger E;Martinez-Jaramillo E;Sam Zhou H;McMasters KM
溶瘤腺病毒（OAds）对于肺癌的治疗非常有希望。然而，基于 OAd 的单一疗法在临床试验中并未有效。因此，必须通过将 OAd 与其他疗法相结合来增强病毒疗法的有效性。在这项研究中，在体外和体内评估了 OAd 与替莫唑胺 (TMZ) 联合治疗肺癌细胞的治疗潜力。 OAd 和 TMZ 联合治疗可协同增强癌细胞死亡；这种增强的癌细胞死亡可以通过三种相关机制来解释：细胞凋亡、病毒复制和自噬。自噬抑制部分保护了癌细胞免受这种联合疗法的影响。这种组合显着抑制了无胸腺裸鼠皮下 H441 肺癌异种移植肿瘤的生长。在这项研究中，我们提供了在肺癌临床试验中测试 OAd 与 TMZ 组合的实验原理。
Oncolytic adenoviruses (OAds) are very promising for the treatment of lung cancer. However, OAd-based monotherapeutics have not been effective during clinical trials. Therefore, the effectiveness of virotherapy must be enhanced by combining OAds with other therapies. In this study, the therapeutic potential of OAd in combination with temozolomide (TMZ) was evaluated in lung cancer cells in vitro and in vivo. The combination of OAd and TMZ therapy synergistically enhanced cancer cell death; this enhanced cancer cell death may be explained via three related mechanisms: apoptosis, virus replication, and autophagy. Autophagy inhibition partially protected cancer cells from this combined therapy. This combination significantly suppressed the growth of subcutaneous H441 lung cancer xenograft tumors in athymic nude mice. In this study, we have provided an experimental rationale to test OAds in combination with TMZ in a lung cancer clinical trial.