| Objective:Through the combined use of different dosing sequence of Endostar joint paclitaxel, observation the effction of vascular normalization made by endostar in Lewis lung tumo model, and discuss the function is similarly existing time window, so as to achieve the best dosing sequence and dose.With a high performance liquid chromatographic for measuring paclitaxel concentrations in the tumor tissue, observe weather the change of two combination therapy group have differences, verify correctnessof the conceive that in normalization window chemotherapy drugs can better enter into the tumor tissue. Methods:This experiment contains two parts. The first part take 30 C57/BL6 mice, randomly divided into 5 groups,6 in each group, through subcutaneous injection logarithmic growth Lewis lung cancer cells levitation liquid to established animal models. In the animal body Nestin three generations through the tumor block, when the tumor size of experimental group grow to certain size, in the basis of recombinant human endostatin injection (10mg/kg) combined paclitaxel (10mg/kg) intraperitoneal injection (respectively give medicine in days1,8 and day 5,12 after recombinant human endostatin injection.), While establishing a control group (1-14 days), alone paclitaxel group(day1,8),endostar group, Endostar were treated 14 days, each day observe the general condition and tumor size in mice, every other day measure tumor size, the next day after give drugs end executed mice by cervical dislocation, complete detachment tumor, detection tumor weight,inhibiting tumor rate, immunohistochemical use TUNEL method to detect cell apoptosis, and calculation cancer cells apoptosis index (AI). The second part take 20 C57/BL6 mice, random into 2 groups, endostar and paclitaxel synchronization using group, use paclitaxel after endostar group,10 in each group, in the day when use paclitaxel,20min later, executed mice, gain tumor tissue, by using high performance liquid chromatography (HPLC) to analyze the difference of paclitaxel concentration changes in tumor tissue between the two groups. Results:Tumor size comparison between control group and endostar and paclitaxel synchronization using group, control group and paclitaxel group, there were no statistically significant difference (P>0.05), control group compared with endostar group are statistically significant (P< 0.05),endostar group and use paclitaxel after endostar group are statistically significant difference (P<0.05),use paclitaxel after endostar group of comparative all other four groups are statistical significance difference (P< 0.05), endostar group and endostar and paclitaxel synchronization using group,use paclitaxel after endostar group compared were no statistically significant difference (P>0.05). use paclitaxel after endostar group have the minimum tumor heavy, average tumor heavy is 2.5815 + 1.6403g, inhibiting tumor rate is 48.09%; control group have the biggest tumor heavy, average tumor heavy is 4.9732 + 1.1122 g, use paclitaxel after endostar group compared with the rest groups, the tumor heavy differences are statistically significant (P< 0.05). Endostar group and endostar and paclitaxel synchronization using group,use paclitaxel after endostar group were no differences between group statistical significance (P>0.05), even found the effect of endostar and paclitaxel synchronization use is worse than Paclitaxel group,endostar group, represent an antagonist role. But use paclitaxel after endostar group has achieved good effect, compared with endostar and paclitaxel synchronization using group,Paclitaxel group,endostar group, differences are statistically significant (P< 0.05). use paclitaxel after endostar group got the highest tumor cell apoptosis index, the average numerical is:50.1200±6.4854%; control group got the minimum tumor cell apoptosis index, the average numerical is: 21.8300±1.8324%, use paclitaxel after endostar group compared with the rest groups, apoptosis index are statistically significant difference (P<0.05). control group and endostar and paclitaxel synchronization using group,paclitaxel group, there were no statistically significant difference (P>0.05), endostar group compared with the rest groups are statistically significant differences (P<0.05). The d1,8 measured paclitaxel concentrations of endostar and paclitaxel synchronization using group,the d12 measured paclitaxel concentrations of use paclitaxel after endostar group comparative differences were not statistically significant (P>0.05). the d5 measured paclitaxel concentrations of use paclitaxel after endostar group compared with the d1 measured paclitaxel concentrations of endostar and paclitaxel synchronization using group difference was statistically significant (P<0.05), compared with measured paclitaxel concentrations in d8 and d12 of the same group, differences was statistically significant (P<0.001).Conclusions: 1. Endostar and paclitaxel synchronization using performance for antagonist role, even in 13 days ago volume exceeded control group, consider combination use paclitaxel and endostar make antitumor angiogenesis treatment excessively, leading to chemotherapy drugs can't better enter into tumor tissue inside.2. On the basis of C57/BL6 mice Lewis lung cancer model, Paclitaxel group curative effect prevents, consider for tumor denormalize blood vessels leading to deficient oxygen inside tumor Chemotherapy drugs can't better distribution to tumor tissue.3. Endostar as antiangiogenic drugs, also has normalization window to make tumor vascular normalized, in this period, endostar with the chemotherapy drug paclitaxel joint use can gain better curative effect. 4. Give paclitaxel after use endostar 4 days can measure the highest concentration in the tumor, afterwards paclitaxel concentrations present degressive type decline, and concentrations is lower than the first day, account for after use endostar 7 days, anti-angiogenic treatment has already effected excessively, lead to chemotherapy drugs into the tumor to organize the concentration into internal tumors gradually decrease.
|
PDF Full Text Request