Treatment Study Of Pleural Injection To Malignant Pleural Effusion Nude Mice Model

Objective:To investigate the treatment effect of pleural injection of recombinant human endostar combined with cisplatin to malignant pleural effusion nude mice model.Methods:We used classic pleural injection method to build malignant pleural effusion (MPE) model, injected Lewis Lung Cancer cell (LLC) into pleural cavity of BALB/c nude mice,3days after injection we randomized40nude mice into4groups, endostar, cisplatin, endostar combined with cisplatin and normal salin control.14days after cell injection, we did cavity injection of endostar, cisplatin, endostar combined with cisplatin and normal salin for3days, then we measured the MPE volume, we did immunehistochemical of CD31for mean blood vessel density, and real-time PCR for two genes of angiogenesis.Results:Based on classic method, the ratio of MPE model was50%, pleural injection for MPE model was stable and safety.14days after the model was built, pleural cavity injection of endostar, cisplatin, endostar combined with cisplatin and normal salin was did for3days,24hours after the third day, nude mices were executed and pleural effusion of each mice was measured. The mean value and standard deviation of each group were:endostar group247.7±89.2ul, cisplatin group447.4±75.3ul, endostar combined with cisplatin group247.7±89.2ul, and503.2±146.6ul for normal salin group. Compared with normal salin group, endostar and endostar combined with cisplatin group could significantly reduce the pleural effusion volume, p<0.05. While there was no significantly difference between cisplatin and normal salin group, endostar and endostar combined with cisplatin group. Compared with normal salin group, mean blood vessel density was significantly reduced by endostar, mean blood vessel density of each group were10.3±2.3for endostar group,27.7±4.6for cisplatin group,11.7±1.9for endostar combined with cisplatin group and28.3±4for normal salin group, compared with normal salin group, endostar or endostar combined with cislpatin group could significantly reduced MPE volume, p<0.05, while there were no significant difference between cisplatin and normal salin group, endostar and endostar combined with normal salin group either. MPE volume of nude mice was positive correlated with MVD. Quantitive real-time PCR analysis results showed that, endostar could reduced angiogenesis gene Vescular epidermal growth factor-a (VEGF-a) expression, but expression of another angiogenesis gene Hypoxia induced factor-1(HIF1-a) elevated at the same time.Conclusion:①MPE model could be made through injecting LLC cells into pleural caivity of nude mice.②Pleural cavity injection of endostar could significantly reduced MPE volume of nude mice, endostar combined with cisplatin could not bring more treatment benefit to nude mice MPE model.③The mechanism of treatment is the anti-angiogenesis effect of the endostar.④The potential anti-angiogenesis mechanism of endostar maybe through inhibiting VEGF-a expression.