Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

Abstract

Abstract. The aim of the present study was to investigate whether low-frequency ultrasound (US)-mediated microvessel disruption combined with docetaxel (DTX) can be used as a novel type of chemoembolization. Mice were assigned to four groups: i) The USMB group, treated with low-frequency US combined with microbubbles (USMB); ii) the DTX group, treated with DTX; iii) the USMB + DTX group, treated with combined therapy; and iv) the control group, which was untreated. Immediately after the first treatment, the average peak intensity (API) on contrast-enhanced US was calculated, and tumors were excised for hematoxylin and eosin (HE) staining. At 2 weeks post-treatment, the tumor volumes and wet weights were calculated, and tumors were excised for immunohistochemistry to calculate apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) values. Immediately after the first treatment, in the DTX and control groups, the tumors demonstrated abundant perfusion enhancement, while in the USMB + DTX and USMB groups, blood perfusion of the tumors was interrupted. Compared with that of the control group, the API was significantly lower in the USMB + DTX USMB groups (all P<0.001). HE staining showed that tumor microvasculature was disrupted into flaky hematomas and severely dilated microvessels in the USMB + DTX and USMB groups. In the DTX and control groups, there was no distinct evidence of the disruption and dilation of blood microvessels. At the end of the treatment, the mean tumor inhibition ratio was 73.33, 46.67 and 33.33% for the USMB + DTX, DTX and USMB groups, respectively. The USMB + DTX group had the highest AI, and the lowest PI and MVD compared with the other groups, although the difference between the USMB + DTX and DTX groups with regard to PI and MVD was not significant (USMB + DTX vs. DTX group, P=0.345 and P=0.059, respectively). In conclusion, as a novel type of chemoembolization, USMB combined with DTX is more effective than USMB or DTX alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis.

Low-frequency and low-intensity ultrasound-mediated microvessel disruption enhance the effects of radiofrequency ablation on prostate cancer xenografts in nude mice

“…Treatment with USMB alone was excluded from the present study for three reasons. Firstly, USMB alone can inhibit tumor growth, however, tumor growth occurs at a slower rate (18,19), which was further confirmed in our previous studies (20), therefore the combination of USMB with other therapies is suggested to treat cancer, rather than alone. Secondly, RFA is able to achieve complete ablation of tumors measuring <3 cm in diameter, however, eradication of larger tumors and avoiding proliferation of residual tumor cells remains a challenge.…”

Improving the Therapeutic Effect of Ultrasound Combined With Microbubbles on Muscular Tumor Xenografts With Appropriate Acoustic Pressure

“…The development of safe and effective antitumor therapies remains a major research hotspot. The use of ultrasound combined with microbubbles (USMB) has recently emerged as a promising method for destroying the tumor vasculature because of its ability to cause complete and persistent cessation of blood flow to the tumor ( Wood and Sehgal, 2015 ; Yang et al., 2016 ), which is mainly considered to occur through vascular dilation ( Wood et al., 2007 ; Wood et al., 2008 ; Levenback et al., 2012 ), thrombosis ( Huang et al., 2013 ; Foiret et al., 2017 ), and ultimate disruption of blood perfusion to the tumor ( Liu et al., 2012 ; Zhang et al., 2018 ). Liu et al.…”

Effect of docetaxel‑loaded lipid microbubble in combination with ultrasound‑triggered microbubble destruction on the growth of a gastric cancer cell line

“…A previous study by Kang et al (35) reported that DLLD combined with UTMD could effectively inhibit the growth of VX2 rabbit liver tumors by deferring proliferation and promoting apoptosis. Studies investigating the effect of DLLD combined with UTMD on the growth of other tumors, such as H22 HCC or MHCC-H hepatocellular carcinoma xenografts and prostate carcinoma xenografts, have also demonstrated that DLLD combined with UTMD was the most effective strategy for the inhibition of tumor cell proliferation and the promotion of apoptosis (28,38,39). Consistent with the aforementioned results, the results of the present study indicated that DLLD combined with UTMD could significantly inhibit DNA synthesis, promote cell accumulation in the G 2 /M phase and stimulate cell apoptosis.…”