Reversal of multidrug resistance in human oral epithelial cancer cells KBV200 by a natural product

doi:10.19803/j.1672-8629.20220534

Abstract

Abstract: Objective To investigate the ability of a natural product EM-E-11-4 at non-cytotoxic concentrations to reverse P-gp-mediated multidrug resistance (MDR) in human oral epithelial cancer cells KBV200 and to reveal the mechanism of action. Methods The effect of EM-E-11-4 on the growth of KB cells and the corresponding resistant cells KBv200 was determined by MTT assay. Using VRP as positive control, the ability of non-cytotoxic concentrations of EM-E-11-4 (2.5, 5, 10 µmol·L-1) with/without such chemotherapeutic agents as paclitaxel vincristine and adriamycin to reverse MDR was evaluated, while the reversal folds (RF) of EM-E-11-4 and VRP were calculated and compared. The effect of EM-E-11-4 and VRP on the accumulation and efflux function of P-gp was studied. Furthermore, the effect of EM-E-11-4 on the ATPase activity of P-gp was measured by Pgp-GloTM kit. Results 10 µmol·L-1 of EM-E-11-4 effectively reversed the MDR-phenotype of KBv200 cells to paclitaxel, vincristine and adriamycin. The RF was 33.8、36.4 and 20.1, respectively. In addition, the P-gp functional study suggested that EM-E-11-4 elevated the intracellular accumulation of adriamycin in a dose-dependent manner. EM-E-11-4 suppressed VRP-stimulated ATPase activity of P-gp in a dose-dependent manner. Conclusion EM-E-11-4 can be a potential agent that can overcome P-gp-mediated MDR by suppressing the transport function of P-gp.

Key words: EM-E-11-4, oral squamous epithelium tumor, multi-drug resistance, P-glycoprotein, paclitaxel, vincristine, adriamycin

CLC Number:

HUANG Wei, WU Ruiqing, SUN Hua, SHI Jiangong, LIU Qian. Reversal of multidrug resistance in human oral epithelial cancer cells KBV200 by a natural product[J]. Chinese Journal of Pharmacovigilance, 2023, 20(4): 403-408.

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