Experimental study of vascular normalization window for tumor induced by bevacizumab and efficacy of bevacizumab plus paclitaxel in lung cancer-bearing mice
ZHANG Jing
ZHANG Wenchao
QIAN Ziqun
GAO Beili
XIANG Yi
Abstract：Objective To explore the time window of bevacizumab to normalize the vascular for tumor and analyze the efficacy of bevacizumab plus paclitaxel in lung cancer-bearing mice.Methods Athymic mice bearing A549 xenografts were constructed.The study can be divided into two parts.In first part, 24 nude mice were randomly assigned into two groups (n=12 per group): control group (intraperitoneal injection of saline) and bevacizumab group (intraperitoneal injection of bevacizumab 5 mg/kg).At four time points after injection (1, 3, 5, 8 d;n=3 at each time point), the volume of tumor and the weight of nude mice were measured.Meanwhile, the levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in tumor tissues were detected by Western blotting and immunofluorescence methods, respectively.In second part, 30 nude mice were randomly divided into four groups: control group (n=5), bevacizumab monotherapy group (n=5), paclitaxel monotherapy group (n=5) and paclitaxel plus bevacizumab group (n=15).On the day of administration or the third and fifth day after administration of bevacizumab, paclitaxel plus bevacizumab group received intraperitoneal injection of paclitaxel with five mice at each time point.The paclitaxel and bevacizumab were administered at doses of 3 mg/kg and 5 mg/kg, respectively.The volumes of tumor were measured at 6 time points including 3, 7, 10, 14, 17, 20 days after administration.The nude mice were killed and the weight of tumor was measured 21 days later.The VEGF and MVD of the tumor were detected by Western blotting and immunohistochemistry.Results In the first part of our study, the tumor growth was suppressed gradually after the treatment of bevacizumab as compared with control group.Tumor volume, VEGF level and MVD reached a nadir at 3 days after bevacizumab administration.In the second part, compared with the control group, bevacizumab in combination with paclitaxel at different time points could suppress the tumor growth with a much significant inhibition effect on day 3 after bevacizumab administration.The average tumor volume, tumor weight, VEGF level and MVD were less in combined administration on day 3 than other combined groups.Conclusion The possible timing of the normalization window was typically 1-3 days after the administration of bevacizumab.The normalization window may provide an opportunity to enhance the effect of paclitaxel with the aid of bevacizumab.
Keywords：BevacizumabPaclitaxelCombined therapyVascular normalization window
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 481-486 )