Research On Enhancement Of Verapamil Reversing Multidrug Resistance Of Tumor Through Ultrasound Irradiating Microbubble

Objective:To explore the effects of reversing the tumor multidrug resistance by ultrasound irradiating microbubbles with verpamil.Methods: The PLGA and VER-PLGA microbubbles were prepared and the neuroblastoma cell line (SK-N-SH/VCR) with multidrug resistance phenotype was established induced with VCR. The cells were divided into six groups according to different treatments : group A:SK-N-SH/VCR, group B: SK-N-SH/VCR+VER(50μg/ml), group C:SK-N-SH/VCR+VER (250μg/ml), group D:SK-N-SH/VCR +ultrasound, group E:SK-N-SH/VCR + PLGA + ultrasound, group F:SK-N-SH/VCR + VER-PLGA(50μg/ml) + ultrasound. RT-PCR and ICC were used to detect the expression level of MDR1 gene and P-gp respectively. And the reversing effects of verapamil on the multidrug resistance of tumor in different groups were evaluated.Results:○1 The PLGA and VER-PLGA microbubbles were prepared successfully, and the envelopment rate was 32%;②The neuroblastoma cell line (SK-N-SH/VCR) with MDR phenotype were established and the resistance index(RI) were 2.3-5.4 times to different chemotherapy drugs comparating to the wild cell line;③Compared with others,the level of mdr1 gene was the most lowest in group F(P<0.05);○4 Compared with that in other 5 groups, the expression levels of P-gp and MDR1 gene were the lowest in group F(P<0.05).Conclusion: Ultrasound irradiating microbubbles could enhance the reversing effects of verapamil on the multidrug resistance of tumors. And this technique provides us a novel way to reverse multidrug resistance of malignant tumors in clinical.