An Experimental Study Of Argon-Helium Cryoablation Combined With Recombinant Human Endostatin In Lung Adenocarcinoma

Objective:The major goal of this study was to evaluate the inhibitory effect of Cryoablation in combination with Endostar on lung adenocarcinoma A549in BALB/c nude mice. Meanwhile, the rates of tumor cell apoptosis, Microvessel Density and the levels of VEGF expression were detected to research the interaction mechanisms of combined therapy. In addition, a comparison of the effects between Cryoablation and cisplatin on A549lung adenocarcinoma models was carried out.Materials and Methods:The transplantation tumor models of A549lung adenocarcinoma were established. All mice were randomized into5groups (n=18) when the largest diameter of tumor reaches at1.0cm. Endostar plus Cryoablation group:mice were given Cryoablation,2hour later mice were given20mg·kg-1of Endostar daily by peritoneal injection for14days. Cryoablation group:mice were given Cryoablation,2hour later mice were given by equal volumes of normal sodium for14day. Endostar group:mice were given20mg·kg-1of Endostar daily by peritoneal injection for14days.cisplatin group:mice were given5mg·kg-1cisplatin by peritoneal injection,2hour later mice were given by equal volumes of normal sodium for14day. Control group:mice were given by equal volumes of normal sodium for14day. We measured the largest diameter and the vertical diameter of tumor at different time points. At the2nd h、14thday、21st day,6mice of every group were executed. The tumors were applied to analysis of rates of tumor cell apoptosis, Microvessel Density and the expression levels of VEGF by IHC.Result:The rates of tumor inhibition of Endostar puls Cryoablation group was higher than that of other groups. Compared with control group, the tumor inhibitory rates of Endostar plus Cryoablation group, Cryoablation group, Endostar group, cisplatin group were57.43%、33.11%、5.41%、30.41%, respectively. In the14th day、21st day,The tumor growth velocity of Endostar puls Cryoablation group was significantly lower than that of other groups, P<0.001. In the2nd day,14th day, the tumor growth velocity of Cryoablation group was significantly lower than that of cisplatin group, P<0.001. In the21st day, the tumor growth velocity of Cryoablation group was lower than that of cisplatin group,P=0.975, there was no statistically significant difference. The rates of tumor cell apoptosis at the2nd hour, Endostar plus Cryoablation group and Cryoablation group were higher than that of other groups,P<0.001. In the14th day.21st day the rates of tumor cell apoptosis of Endostar plus Cryoablation group. Cryoablation group and cisplatin group were significantly higher than that of other groups, P<0.001. In the2nd day,14th day,21st day, The levels of VEGF expression and Microvessel Density in Endostar plus Cryoablation group was lower than the other groups, P<0.001.Conclusion:1. Endostar obviously enhances the treatment efficacy of Cryoablation on lung adenocarcinoma A549in BALB/c nude mice.2. The underlying mechanisms may involve in the cooperative effect of Endostar and Cryoablation on synergistically promoting tumor cell apoptosis. And we should also consider that Endostar inhibited angiogenesis by down-regulating the expression of VEGF for the potenial synergistic mechanisms.3. The inhibitory effect of Cryoablation group on A549lung adenocarcinoma models was equivalent to that of cisplatin group.