Caveolin-1 as a biomarker to predict therapeutic effect of low-frequency ultrasound combined with SonoVue on prostate cancer in nude mice model.

BACKGROUND

Caveolin-1 is a major structural component of cell membrane invaginations. Over-expression of caveolin-1 is closely related to the tumorigenesis and progression of prostate cancer. Recently, contrast microbubbles in combination with ultrasound are being investigated for their therapeutic applications in tumor cells. However, the response of caveolin-1 after low-frequency ultrasound and SonoVue treatment in animal model is unclear.

OBJECTIVE

The goal of this study was to evaluate the effect of 80 kHz ultrasound and/or SonoVue on caveolin-1 expression and secretion in DU145 prostate tumors in nude mice.

METHODS

Six-week-old BALB/c male nude mice were subcutaneously injected with DU145 cells in the right flank to establish a prostate cancer model, which were randomly divided into four groups (n=8 each): control group (sham-ultrasound exposure), SonoVue group, 80 kHz ultrasound group, 80 kHz ultrasound combined with SonoVue group. Tumor volumes and wet weights were measured, and the tumor volume curve was obtained as well. The mice were euthanized 21 days after treatment. Specimens of the tumor tissues were assessed the expression of caveolin-1 by immunohistochemistry and Western blot. The serum concentrations of caveolin-1 were detected by ELISA.

RESULTS

Treatment with ultrasound alone produced tumor volumes and weights reduction compared with control and SonoVue group. Combined ultrasound and SonoVue treatment produced greater tumor regression than either treatment alone (p < 0.05). Serum caveolin-1 concentrations were lower in the combination of ultrasound and SonoVue group than they were in control group (p =0.005), and had some certain correlation with tumor growth (wet weight) (r =0.507), although the difference was not statistically significant (p=0.199). Ultrasound alone treatment only slightly reduced the caveolin-1 concentrations in comparison with the control, and the difference was not statistically significant (p=0.125). The ultrasound-treated mice showed significant reduction in expression levels of caveolin-1 protein, compared with the control (p < 0.05). Levels of caveolin-1 were further reduced when combined with ultrasound and SonoVue as compared to the control (p < 0.01).

CONCLUSIONS

Our results suggest that 80 kHz ultrasound have antitumor effect and the effect could be further strengthened by the combination of SonoVue. Down-regulating the expression of caveolin-1 is likely a potential biomarker of response to ultrasound and SonoVue treatment in prostate cancer mouse model.