Experimental Study of Ultrasound on MDR in a Human Tumor in Vivo

摘要

Objective To evaluate the potential efficacy of low-intensity ultrasound (US) in combination with anticancer drugs to reverse multidrug resistance (MDR) in nude mice. METHODS A total of 40 male and female athymic nude mice were inoculated subcutaneously with 5×10~6 HepG_2/ADM and HepG_2 cells. Ultrasound with pulsed irradiation at an average intensity of 0.5 W/cm~2 was given to the tumor area 10 min after administration of adriamycin (ADM). The tumor 3 dimensional diameters were measured by calipers before and after treatment, and the tumor growth indexes (TGI) calculated. RT-PCR was used to detect the gene levels of the HepG_2/ADM cells. Immunohistochemical analyses for MDR proteins were conducted on the tumor tissues. RESULTS The ultrasonic treatment resulted in an average reduction in the tumor volume of 62% one month later. The relative mRNA levels of MDR1 and MRP were significantly different among the following 4 groups: untreated group as control, ADM treated; US treated; and ADM plus US treated. The mRNA levels of mdr1 and mrp were down-regulated in the US groups compared to those of the non-ultrasound groups by multiple comparisons. The relative mRNA levels of Irp expression were not significantly changed. The results of immunohistochemistry indicated that tumor tissue from animals treated with US had remarkably low mdr1 and mrp expression. CONCLUSION The results showed that low-intensity US can effectively reduce the size of adriamycin-resistant human hepotacarcinoma in a nude mouse model, and support the efficacy of US to overcome multiple mechanisms of drug resistance.