Enhanced phosphatidylserine-selective cancer therapy with irradiation and SapC-DOPS nanovesicles.

Autor:	Davis HW; Division of Hematology/Oncology, Translational Research Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Vallabhapurapu SD; Division of Hematology/Oncology, Translational Research Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Chu Z; Division of Hematology/Oncology, Translational Research Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Vallabhapurapu SL; Division of Hematology/Oncology, Translational Research Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Franco RS; Division of Hematology/Oncology, Translational Research Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Mierzwa M; Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Kassing W; Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Barrett WL; Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Qi X; Division of Hematology/Oncology, Translational Research Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2019 Jan 25; Vol. 10 (8), pp. 856-868. Date of Electronic Publication: 2019 Jan 25 (Print Publication: 2019).
DOI:	10.18632/oncotarget.26615
Abstrakt:	Normal living cells exhibit phosphatidylserine (PS) primarily within the intracellular leaflet of the plasma membrane. In contrast, viable cancer cells have high levels of PS on the external surface, and exhibit a broad range of surface PS, even within specific types of cancer. Agents that target surface PS have recently been developed to treat tumors and are expected to be more effective with higher surface PS levels. In this context, we examined whether surface PS is increased with irradiation. In vitro irradiation of cancer cell lines selected surviving cells that had higher surface PS in a dose- and time-dependent manner. This was more pronounced if surface PS was initially in the lower range for cancer cells. Radiation also increased the surface PS of tumor cells in subcutaneous xenografts in nude mice. We found an inverse relationship between steady state surface PS level of cancer cell lines and their sensitivity to radiation-induced cell death. In addition, serial irradiation, which selected surviving cells with higher surface PS, also increased resistance to radiation and to some chemotherapeutic drugs, suggesting a PS-dependent mechanism for development of resistance to therapy. On the other hand, fractionated radiation enhanced the effect of a novel anti-cancer, PS-targeting drug, SapC-DOPS, in some cancer cell lines. Our data suggest that we can group cancer cells into cells with low surface PS, which are sensitive to radiation, and high surface PS, which are sensitive to SapC-DOPS. Combination of these interventions may provide a potential new combination therapy. Competing Interests: CONFLICTS OF INTEREST X. Qi is listed as an inventor on the patent for SapC-DOPS technology that is the subject of this research. Consistent with current Cincinnati Children's Hospital Medical Center policies, the development and commercialization of this technology has been licensed to Bexion Pharmaceuticals, LLC, in which Dr. Qi, holds a minor (< 5%) equity interest. The other authors declared no conflicts of interest.
Databáze:	MEDLINE
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