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

Virology Journal

Heshan Sam Zhou¹  Kelly M McMasters²  Xiao-Mei Rao⁴  Robin Zhao²  Serena Lian²  Pei-Hsin Cheng³ 

[1] Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA;Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA;Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA;James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA

关键词: Rapamycin;    Autophagy;    Cyclin E;    Replication;    Oncolytic adenovirus;   

Others  :  821354
DOI  :  10.1186/1743-422X-10-293

 received in 2013-04-29, accepted in 2013-08-21,  发布年份 2013

【 摘 要 】

Background

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.

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.

【 授权许可】

   
2013 Cheng et al.; licensee BioMed Central Ltd.

【 图 表 】

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