The experimental study of the inhibitory effect of self-made nanobubbles combined with cisplatin mediated by ultrasound on H22 neoplasms of mice / 中华超声影像学杂志

ABSTRACT

Objective To investigate the optimal ultrasound exposure parameter on H22 neoplasms of mice meditated by ultrasound exposure combined with self‐made nanobubbles ,and then observe their therapeutic effect combined with cisplatin and their possible mechanism of anti‐tumor . Methods Thirty mice engrafts models with subcutaneous H22 neoplasms were established and divided into 6 groups randomly ,which received ultrasound exposure at different intensity and exposure time . The contrast enhanced ultrasound imaging ( CEUS ) was performed in every group at the four time points of before treatment and at 0 h ,24 h ,72 h after treatment . To obtain the optimal ultrasound parameters ,the tumor inhibitory effect was assessed by enhanced intensity ( EI) and microvascular density ( MVD) . The H22 tumor were treated by ultrasound exposure nanobubbles combined with cisplatin to observe their tumor growth inhibition rate ,and the microvessels density and nuclear associated antigen Ki‐67 proliferation index were measured by immunohistochemical staining . Results There was a statistically difference in enhanced intensity (EI) between the experimental groups and control group ( P < 0 .05) . With the increasing of ultrasound intensity and exposure time ,the tumor inhibitory effect was more obvious ,with an increasing side reactions . Except the simple ultrasound group ,there was a statistical difference in tumor inhibition ,the mean MVD and the tumor cell proliferation index (KI‐67) between control group and the other ultrasound therapy groups ( P<0 .05) . The tumor inhibitory rate was the highest ( tumor inhibition rate 70 .0% ) and the mean MVD and KI‐67 expression were the lowest ( P <0 .05) in the combination group comparing with the others . Conclusions The ideal ultrasound exposure parameter of tumor inhibition showed that exposure intensity chose 1 W/cm2 and exposure time chose 1 min or 3 min intermittence . The ultrasound exposure self‐made nanobubbles combined with cisplatin could enhance the tumor inhibitory effect .Its mechanism may be related to the decrease of microvascular density ,the inbition of tumor cell proliferation and the increase of tumor cell necrosis .