Experimental study on the therapeutic effects of cryoablation combined with sorafenib and interleukin 2 on renalcancer transplantation tumor in nude mice

doi:10.3969/j.issn.1002-7386.2018.11.007

Abstract：Objective To investigate the therapeutic effects of cryoablation combined with sorafenib and interleukin 2 on renal cancer transplantation tumor in nude mice, and to explore possible action mechanism. Methods The subcutaneous transplantation tumor models of human renal cancer ( Renca) were established in 50 nude mice. The nude mice were randomly divided into control group, cryoablation group, sorafenib group, interleukin 2 group and combination treatment group, with 10 mice in each group. At four weeks after inoculating, these nude mice were sacrificed and the tumor tissues were separated. The weight of tumor tissues and inhibition rates of tumor growth were calculated and compared. The apoptosis rates of tumor cells, the percentages of T lymphocyte subpopulation and natural killer ( NK ) cells proportion were detected by flow cytometry. The serum levels of vascular endothelial growth factor (VEGF), VEGFR 2, hypoxia-inducible factor 1α(HIF 1α) were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of VEGF, VEGFR 2 and HIF 1αproteins in tumor tissues were detected by Western Blot. The microvessel density ( MVD) of tumor tissues was detected by immunohistochemical SP method. Results The tumor weigh, serum levels of VEGF, VEGFR 2, HIF 1α, expression levels of VEGF, VEGFR 2, HIF 1α proteins and MVD of tumor tissues in combination treatment group were significantly lower than those in the other groups (P<0. 05). However the inhibition rates of tumor growth, apoptosis rates of tumor cells and the percentages of CD4 + T, CD8+ T and NK cells in combination treatment group were significantly higher than those in the other groups (P<0. 05). Moreover the survival time of mice in combined treatment group was significantly longer than that in the other groups (P<0. 05). Conclusion The cryoablation combined with sorafenib and interleukin 2 can inhibit the growth of renal cancer transplantation tumor in nude mice through anti-angiogenesis and immune-enhancement.