| Abstract:Objective:It is well known that lung cancer is one of the most common malignant tumor in today’s world. In recent years, under the continuous efforts of medical researchers, for the relevant treatment of lung cancer constantly appear and obtained obvious effects. Endostatin in combination with chemotherapy drugs is a common clinical treatment of lung cancer, Preliminary experiment showed that the better sequence of Endostain joint paclitaxel is continuously using Endostain for 3 to 5 days then to inject paclitaxel. However, it remains to be further research to definite the best "Time Window", and our experiment is to study this direction. In this study, we get the answer by accumulating volume of tumors, according tumor weight to draw the growth curve, using high-performance liquid chromatography (HPLC) to detect the concentration of paclitaxel and Taking advantage of Small animal imaging technology directly observed tumor angiogenesis situation in the organization, further pushing the result. Methods:This study contains two parts. The first part take 48 C57/BL6 mice, randomly divided into 8 groups, each group has 6 mice, establishing Lewis lung cancer animal model by subcutaneous injection logarithmic phase Lewis lung cancer cells, extending the three generations in vivo by tumor block. when the tumor sizes of experimental groups grow to certain size, then began to drug intervention. On the basis of endostatin (10mg/kg) in combination with paclitaxel basis (10mg/kg) to intraperitoneal injection, continuously injecting endostain for eight days, each group were respectively intraperitoneal injected the paclitaxel after continuously endostain for 1,2,3,4,5,6,7,8 days. Observing the general conditions and tumor formation rate of mices in each group every day, measuring the mice tumor sizes every other day, the mice were killed by cervical vertebra dislocation after finish intraperitoneal injection, complete stripping tumor, measuring tumor weight and inhibitory rate, through immunohistochemistry to determine the tumor microvascular maturity and lack of oxygen levels, by using high performance liquid chromatography (HPLC) to measure the concentrations of paclitaxel in each tumor tissue group. The second part:according to the first part of the experimental data, statistics suggest that the best anti-tumor is Group5. Taking 3 mice, divided into 3 groups,1 mice each group:each group were respectively intraperitoneal injected the paclitaxel after continuously endostain for 3,4,5 days. Taking advantage of Small animal imaging technology directly observed tumor angiogenesis situation in the organization, further pushing the result. Results: The first part:Comepared with Group 1 (injected the paclitaxel after continuously endostain for 1), Group2(injected the paclitaxel after continuously endostain for 2), Group6(injected the paclitaxel after continuously endostain for 6), Group7(injected the paclitaxel after continuously endostain for 7), Group8(injected the paclitaxel after continuously endostain for 7), Group3 (injected the paclitaxel after injected the paclitaxel after continuously endostain for 3), volume mean of Group4 (injected the paclitaxel after continuously endostain for 4), Group5 (injected the paclitaxel after continuously endostain for 5) are low, the difference has statistically significant, P< 0.05. Group3, Group4 and Group5 have no statistically significant differences, P> 0.05. Eight groups there was no statistically significant difference in mice tumor weight, select Group8 as the control Group, it can be seen that the inhibitory rate of Group3, Group4 and Group 5 were better than other groups, which were 20.5%,24.66% and 23.74% respectively. Through Immunohistochemistry measure a-SMA:compared with Group 1, Group2, Group6, Group7 and Group8, a-SMA mean of Group3, Group4 and Group5 were higher, the difference had statistically significant, P< 0.05, Group4 compared with Group5 was significant difference, P<0.01, there was no statistically significant difference compared with the Group3, P> 0.05; Through Immunohistochemistry measure HIF-la:compared with Group, Group2,Group6, Group7 and Group8, HIF-la mean of Group3> Group4 and Group5 were lower, the difference had statistically significant difference, P< 0.05, Group4 compared with Group5 was no significant difference, P>0.05. Using HPLC technology to measure concentration of Paclitaxel:compared with Group 1 and Group2 group, Group6, Group7 and Group8, drug concentration means of Group3, Group4 and Group5 were higher, the difference had statistically significant, P< 0.05. Group3, Group4 and Group5 had no statistically difference, P> 0.05. The second part of the experiment: The average optical density value of group A was 489.17, the average optical density value of group B was 356.98, the average optical density value of group C was 436.07. Conclusion:1 Endostain as an anti-angiogenesis drug has a short and reversible tumor blood vessels normalization time, over this period inhibitory effect of endostar with paclitaxel would be weakened. 2. Time window of endostain combination with paclitaxel is 3-5 days, in this period, lack oxygen level was improved, tumor vascular structure and function would be maturing.3 The best time of time window is the fourth days. |
PDF Full Text Request