The Effects Of Antimicrobial Peptides Temporin-1CEa On Breast Cancer Multidrug Resistant Cell MCF7/ADR

Cancer cells have developed the resistance in response to treatment, the reason for whichwere widely studied and found that the over-expression of cell membrane transporterP-glycoprotein (P-gp) could extrude a variety of hydrophobic drugs. This was the mainlimitations for the efficient chemotherapy, but antimicrobial peptides can overcome theselimitations. MAPs exerted selective cytotoxicity to cancer cells, but almost no or less toxicityto the human body, therefore MAPs exhibited the potential to be as novel type of anticanceragents. In this study, Temporin-1CEa was separated from the skin secretions of the Chinesebrown frog Rana chensinensis. The effects of antimicrobial peptides Temporin-1CEa againstbreast cancer multidrug resistant cell MCF7/ADR were also discussed.The inhibition effects of antimicrobial peptides Temporin-1CEa on breast cancersensitive cells MCF-7and resistant cells MCF7/ADR were detected by MTT assay;Temporin-1CEa had selective action for two breat cancer cells by the methods of LDH assayand Annexin V-FITC single staining assay; and then the target of Rho-Temporin-1CEa wasobserved by Confocal Laser Scanning microscopy. And in order to explore the mechanism ofantimicrobial peptides against resistant cells, the PS and the net charge content under thesurface of the membrane of MCF-7and MCF7/ADR were both measured, also the expressionof P-glycoprotein of MCF7/ADR was also examined.MTT results showed that Temporin-1CEa inhibited the growth of both sensitive cells andMDR cancer cells, and found that Temporin-1CEa was more sensitive to MCF7/ADR; LDHresults showed Temporin-1CEa had selectivity for both cancer cells, and were non-toxic fornormal breast cells and normal skin cells; Confocal Laser Scanning microscopy resultsshowed that Temporin-1CEa and P-gp co-localize on the membrane of almost intactMCF7/ADR cancer cells. Flow cytometry results showed that PS and the net charge contentof the cell membrane MCF7/ADR cells were more than MCF-7cells, which madeTemporin-1CEa bind with resistant cells more easily; P-glycoprotein content of MCF7/ADRcells was also more than that in MCF-7cells, and MCF7/ADR cells that survivedTemporin-1CEa treatment had decreased P-gp expression; Inhibitors experimental resultsshowed that the inhibition of P-glycoprotein reduced the Temporin-1CEa effect inMCF7/ADR cells. Reversal experimental results showed that, antimicrobial peptidesTemporin-1CEa can reverse MCF7/ADR cells resistance to anticancer drugs, and makeMCF7/ADR cells more susceptible to doxorubicin.