Investigation of combination therapy modes of bevacizumab and paclitaxel for NSCLC in vivo

ABSTRACT

To explore the optimized scheduling and mode of administration of bevacizumab combined with paclitaxel in vivo. Human lung cancer A549 cells was subcutaneously injected in to 40 nude mice, which were stochastically divided into five groups group A, physiological saline as control group, group B, paclitaxel 10mg/kg/d, i.v.bolus, q5d×4; group C, paclitaxel [10mg/kg/d] 24 hours prior to bevacizumab [5mg/kg/d], i.v.bolus, q5d×4; group D, paclitaxel [10mg/kg/d] 24 hours after to bevacizumab [5mg/kg/d], i.v. bolus, q5d×4; group E, paclitaxel [10mg/kg/d] 24 hours later following bevacizumab [1.25mg/kg/d], i.v. bolus, q5d×4. The tumor growth and side-effects of each therapy group were investigated. Micro vessel density [MVD], Evans blue [EB] quantitative detection, and EB content were analyzed and the tumor vascular permeability was calculated. Circulating endothelial progenitor cells [CEPs] were marked by CD31/CD133/CD117 positive cells and measured by flow cytometry. Lower tumor volume, lower tumor weight, and higher inhibitory rates of tumor growth were witnessed in combination therapy groups [group C, D and E] in comparison with control group [P<0.05]. The tumor growth inhibitory rates in groups B, C, D and E were 7.44%, 55.43%, 66.22%, and 75.79%, respectively. The side-effects in combined therapy group were tolerated. Compared with the control group, MVD in all treatment groups were decreased significantly [P<0.05]. Furthermore, MVD in combined therapy groups were decreased than single therapy [P<0.05]. The EB content of tumor tissues in combined therapy groups was significantly upregulated in comparison with the control group [P<0.01]. The changes of CEPs in combined therapy groups were notably higher than that in control group. Bevacizumab has synergetic inhibitory effect with paclitaxel against lung aden carcinoma A549 cell xenografts in mice by inhibiting angiogenesis of the tumor. Different modes of administration of bevacizumab with paclitaxel showed various anti-tumor and anti-angiogenesis effectiveness, in which bevacizumab prior to paclitaxel was better than paclitaxel prior to bevacizumab and consecutive administration of bevacizumab was better than administration of bevacizumab at intervals