Co-delivery of metformin enhances the anti-multidrug resistant tumor effect of doxorubicin by improving hypoxic tumor microenvironment.

08:00 EDT 16th May 2019 | BioPortfolio

Summary of "Co-delivery of metformin enhances the anti-multidrug resistant tumor effect of doxorubicin by improving hypoxic tumor microenvironment."

Doxorubicin (DOX) is a first-line chemo drug for cancer therapy, yet it fails to treat multidrug resistant tumors. Hypoxia is a major reason causing failure in chemotherapy. Particularly, hypoxia up-regulates its responsive transcription factor - hypoxia-inducible factors (HIF) to induce the overexpression of drug resistant genes. Metformin (MET) is recently found to cooperate with DOX against multiple tumors. As a mitochondrial inhibitor, MET could suppress tumor oxygen consumption, and thereby modulate hypoxic tumor microenvironment. In this study, we used cationic liposomes to co-deliver both DOX and MET for treating multidrug resistant breast cancer cells - MCF7/ADR. Faster release of MET enhanced cytotoxicity of DOX through attenuating hypoxic stress both in vivo and in vitro. MET reduced the cellular oxygen consumption and inhibit HIF1α and P-glycoprotein (Pgp) expression in vitro. In addition, the dual drug loaded liposomes increased tumor targeting and intratumoral blood oxygen saturation, which suggested that the tumor reoxygenation effect of MET facilitated to exert its synergistic activity with DOX against MCF7/ADR xenografts. In general, our study represents a feasible strategy to boost therapeutic effect in treating multidrug resistant cancer by improving the hypoxic tumor microenvironment.


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This article was published in the following journal.

Name: Molecular pharmaceutics
ISSN: 1543-8392


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