Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound

Abstract

The aim of the present study was to investigate the underlying mechanism(s) involved in reversing multidrug resistance (MDR) of SK-N-SH/MDR1 by low-intensity pulsed ultrasound (LIPUS). Membrane alteration of SK-N-SH/MDR1 cells exposed to LIPUS was analyzed by scanning electron microscopy (SEM). Immunofluorescence and western blotting were used\ to detect changes in the expression of the MDR-related proteins P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1) and glutathione-s-transferase-π (GST-π) after the optimum ultrasonic. The optimum ultrasonic conditions were 0.3 MHz, 1.0 W/cm², 40 sec and the chemosensitivity of SK-N-SH/MDR1 cells was significantly increased (P<0.05). The optimum ultrasonic-induced perforation of the irradiated cell membranes was observed by SEM. The expression of P-gp was significantly decreased in the group treated by optimum ultrasonic (P<0.05), but not the expressions of MRP1 or GST-π (P>0.05). We demonstrated that LIPUS effectively reverses the MDR of SK-N-SH/MDR1, presumably via augmenting membrane permeability and decreasing the P-gp expression of SK-N-SH/MDR1.