Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells.
Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells.
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DOI：
10.1186/1743-422x-10-293
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发表时间：
2013-09-23
期刊：
影响因子：
4.8
通讯作者：
Zhou HS
中科院分区：
文献类型：
--
作者：
Cheng PH;Lian S;Zhao R;Rao XM;McMasters KM;Zhou HS
溶瘤腺病毒（Ads）与化疗药物联合应用已显示出良好的治疗效果，被认为是一种潜在的肿瘤治疗方法。我们以前已经表明，自噬可能会产生分解的细胞分子，这些分子可以用作营养，以支持癌细胞中的病毒复制。在这项研究中，我们评估了一种独特的组合，新的溶瘤的Ad-cycE与雷帕霉素，自噬诱导剂和一线化疗药物。评估溶瘤Ad-cycE和自噬诱导剂雷帕霉素的组合的增强的抗肿瘤作用。我们还评估了雷帕霉素和Ad-cycE对癌细胞活力的联合作用。用Calcusyn（Biosoft，Ferguson，MO）分析Ad-cycE和雷帕霉素之间的相互作用。我们发现，雷帕霉素诱导自噬，增强Ad E1 A的表达和增加Ad溶瘤复制。雷帕霉素与Ad-cycE联合应用比单独应用具有更强的细胞毒作用。分析的数据表明，Ad-cycE和雷帕霉素组合具有显著的协同抗肿瘤作用。我们的研究为载体的发展提供了新的见解，并证明了自噬在腺病毒复制中的新作用。自噬诱导的化疗和溶瘤病毒疗法的组合可能是改善未来癌症治疗的新方法。
Combination of oncolytic adenoviruses (Ads) and chemotherapy drugs has shown promising therapeutic results and is considered as a potential approach for cancer therapy. We previously have shown that autophagy may generate decomposed cellular molecules that can be used as nutrition to support virus replication in cancer cells. In this study, we evaluated a unique combination of the novel oncolytic Ad-cycE with rapamycin, an autophagy inducer and first-line chemotherapeutic drug. The combination of oncolytic Ad-cycE and the autophagy inducer rapamycin was assessed for enhanced antitumor effect. We also evaluated the combined effects of rapamycin and Ad-cycE on cancer cell viability. The interaction between Ad-cycE and rapamycin was analyzed with Calcusyn (Biosoft, Ferguson, MO). We show that rapamycin induces autophagy, enhances Ad E1A expression and increases Ad oncolytic replication. Combination of rapamycin and Ad-cycE elicits stronger cytotoxicity than single treatment alone. The analyzed data indicates that the Ad-cycE and rapamycin combination has a significantly synergistic antitumor effect. Our study provides a new insight into vector development and demonstrates the novel roles of autophagy in adenovirus replication. The combination of autophagy-induced chemotherapy and oncolytic virotherapy may be a new approach to improve future cancer treatment.