The Inhibition Of Rh-endostatin (YH-16) In Combination With Radiotherapy On Lung Adenocarcinoma A549 In Mice And Its Mechanisms

Objective The major goal of this study was to evaluate the inhibitory effect of Endostar in combination with radiotherapy on lung adenocarcinoma A549 in BALB/c nude mice. Meanwhile, the rates of tumor cell apoptosis and the levels of bFGF mRNA and VEGF expression were detected to research the interaction mechanisms of combined therapy. In addition, a comparison between the effect of Endostar plus radiotherapy and cisplatin plus radiotherapy on A549 lung adenocarcinoma models was carried out.Methods The transplantation tumor models of A549 lung adenocarcinoma were established. All mice were randomized into 5 groups(n=6)when the largest diameter of tumor reaches at 1.0 cm. Endostar group: mice were given 10 mg·kg-1 of Endostar daily by peritoneal injection for 14 days. Control group:mice were given by equal volumes of normal sodium for 14 day. Radiotherapy group: mice were treated by 10Gy electron beam irradiation at the third day. Endostar plus radiotherapy group: mice were given daily by peritoneal injection with 10 mg·kg-1 of Endostar for 14 day, in addition, they were given 10Gy electron beam irradiation at the third day. DDP plus radiotherapy group : two hours before mice were given 10Gy electron beam irradiation at the third day, they were given 3mg·kg-1 cisplatin by peritoneal injection.We measured the largest diameter and the vertical diameter of tumor at different time points. At the 16th day, all mice were executed. The tumors were applied to analysis of rates of tumor cell apoptosis, and the expression levels of bFGF mRNA by RT-PCR and VEGF by IHC were also detected in the first four groups.Results The rates of tumor inhibition in both combined treatment groups were higher than other groups . Compared with control group, the tumor inhibitory rates of Endostar as a single agent, radiotherapy alone, Endostar plus radiotherapy group and DDP plus radiotherapy group were 26.6%,31.8%, 41.1%,47.7%,respectively. The tumor growth velocity of combined group with Endostar and radiotherapy was a little higher than that of DDP and radiotherapy, but there was no statistically significant difference. And the rates of tumor cell apoptosis in two combined treatment groups were higher than other groups . The apoptosis rates of control group, Endostar as a single agent, radiotherapy alone, Endostar plus radiotherapy group and DDP plus radiotherapy group were (12.20±1.11)%, (14.75±0.91) %,(16.48±0.85)%,(20.52±1.89) %, (24.45±1.48)%,respectively ( P<0.01). The levels of bFGF mRNA and VEGF expression in combined treatment group with Endostar and radiotherapy were lower than the first three groups.Conclusion 1.Endostar obviously enhances the treatment efficacy of radiotherapy on lung adenocarcinoma A549 in BALB/c nude mice. The underlying mechanisms may involve in the cooperative effect of Endostar and radiotherapy on synergistically promoting tumor cell apoptosis. And we should also consider that Endostar inhibited angiogenesis by down-regulating the expression of the bFGF mRNA and VEGF for the potenial synergistic mechanismse.2.The inhition effect of DDP plus radiotherapy on A549 lung adenocarcinoma models was equivalent to that of Endostar plus radiotherapy.