Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells.
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.
Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA. hszhou01@louisville.edu.
Pei-Hsin
PH
Cheng
Serena
S
Lian
Robin
R
Zhao
Xiao-Mei
XM
Rao
Kelly M
KM
McMasters
Heshan Sam
HS
Zhou
D000256:Adenoviridae / Q000254:growth & development* / Q000502:physiology; D001343:Autophagy; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D050504:Oncolytic Viruses / Q000254:growth & development*; D020123:Sirolimus / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication
D020123:Sirolimus