Synergistic Anticancer Mechanism of α-Helical Peptides and Doxorubicin/epirubicin

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  Low uptake of chemical anticancer drugs into tumors cells can be an obstacle factor for their efficacy; in addition,the toxicity of chemotherapy drugs is also a major cause of mortality of cancer patients.In this study,combinational usages with α-helical peptides HPRP-A1/HPRP-A2,anticancer activities of chemical drugs DOX and EPI were synergistically increased in vitro against different cancer cell lines and in a HeLa xenograft model in BALB/c nude mice.Combinational usage of peptide and chemical drug can produce the following results including significant cell growth inhibition,cell cycle arrest and apoptosis even under a concentration of drugs which barely showing cytotoxicity when used alone.The synergy mechanism was studied by detecting the apoptosis pathway and morphologic changes of HeLa cell membrane.We proved that synergy of peptides and chemotherapy drugs could be explained by an enhanced apoptosis mechanism.HPRP-A1 enhanced DOX-mediated apoptosis and seemed to be caspase-dependent and to be involved both the extrinsic and intrinsic parts of the caspase cascade in HeLa cells.Through cell cycle analysis and flow cytometry,apoptosis of cells was demonstrated to be correlated with the induction of cell cycle arrest in G2/M which is the same blocking cellular phase with DOX used alone.Combined application of HPRP-A1 and DOX with low concentrations exhibited significant results to treat HeLa tumors on a mouse xenograft model,which represents great potentials of drug combinations on clinical practices.
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