Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells

自噬诱导剂雷帕霉素与溶瘤腺病毒联合应用增强癌细胞抗肿瘤作用

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作者:Pei-Hsin Cheng, Serena Lian, Robin Zhao, Xiao-Mei Rao, Kelly M McMasters, Heshan Sam Zhou

Background

Combination of oncolytic adenoviruses (Ads) and chemotherapy drugs has shown promising therapeutic

Conclusions

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.

Methods

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).

Results

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. Conclusions: 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.

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