Experimental Study Of The Efficacy And Vascular Normalization Time Window Of Bevacizumab In Combination With Pemetrexed In Lung Adenocarcinoma Mice Model

Objective To explore the vascular normalization time window of bevacizumab and analyze the efficacy of bevacizumab in combination with pemetrexed in lung adenocarcinoma mice model.Methods 24 mice,which were successfully constructed of A549 xenografts,were randomly divided into six groups:control group(n=4,intraperitoneal injection of saline),pemetrexed monotherapy group(n=4,intraperitoneal injection of pemetrexed 50mg/kg),bevacizumab monotherapy group(n=4,intraperitoneal injection of bevacizumab 15mg/kg),in other 3 groups(n=4)were intraperitoneal injected of bevacizumab 15mg/kg firstly and then at three time points(0,3,5d)were injected of pemetrexed 50mg/kg.All of the mice were killed and weighed the tumor after 2 weeks later.Observing the tumor vessel density and tumor cell proliferation activity by immunohistochemistry.Results Compared to control group,it would be effective no matter monotherapy with pemetrexed or bevacizumab or pemetrexed plus bevacizumab treatment,however,the tumor were significantly inhibited in the group of day 2 after bevacizumab administration and the tumor cell proliferation activity was greatly suppressed.Conclusion The vascular normalization time window of bevacizumab was possibly 2 days,and it will be achieved the best curative efficacy when pemetrexed was used after 2 days of bevacizumab in mice with A549 xenografts.