Abstract

Background: The number of deaths from prostate cancer is still high due to ATP Binding Cassette (ABC)-Mediated Multidrug Resistance (MDR). Overexpression of ABC transporters causes multidrug resistance in most prostate cancer chemotherapies. P-glycoprotein (P-gp) is one of the common drug transporters associated with MDR. There are no drugs approved by FDA to reverse MDR (inhibiting P-gp) in prostate cancer. This study utilized drug combination to reduce MDR expression by using 3-Bromopyruvate (3-BPA) to potentiate the therapeutic effect of SC-514. SC-514 is a relatively new hydrophobic dug, which has been shown to have anti-cancer effects via inhibition of NF-KB-dependent gene expression in cancer cells. 3-BPA is an alkylating agent, glycolytic inhibitor, and an anticancer drug that has a great potential to enhance the effects of anticancer drugs.

Aim of study: This study aimed to reduce acquired and intrinsic ABC-mediated multidrug resistance (MDR) by increasing the drug efficiency of SC-514 via drug combination with 3-BPA.

Method: Cell titer glow assay, multidrug resistance efflux assay, immunofluorescence assay and ELISA assay were utilized to investigate the drug efficiency of SC-514 in combination with 3-BPA and the number of drug resistance GR-PC-3 cells and PC-3 cells after treatment.

Results: Combination of SC-514 and 3-BPA significantly decreased intracellular ATP and the number of MDR cells in GR-PC-3 and PC-3 prostate cancer cells. SC-514 and/3-BPA treatments reduce NF-KB activation, IL-6 expression, and BCL2 expression. However, SC-514 and/3-BPA treatments increase the expression of Bax. 

Conclusion: Combination of SC-514 and 3-BPA increased the therapeutic effect of SC-514 in prostate cancer treatment. The anticancer activities of SC-514 and 3-BPA in combination is promising for future drug development and drug combinations to completely reverse MDR in prostate cancer treatments.

Keywords

multidrug resistance, SC-514, drug combination, toxicity, potentiate, prostate cancer, malignancy, deprivation treatment, castration resistant, cancer cells, metabolic reprogramming, clinical applications, minimum fluctuation, drug activity, efflux transporters, P-glycoprotein, metastasis