| Objective: To study the radiosensitization recombinant human endostatin forhuman lung adenocarcinoma and investigate its mechanisms.Methods:To establish a transplanted tumor model of human lung adenocar-cinoma cell line973in nude mice. Then the tumor bearing mice were randomlydivided into four groups: control group,10Gy group, Endostar group and Endostarcombined with10Gy in treatment group. The irradiation groups, were respectivelyreceived single fraction irradiation on the seventh day of using Endostar, the dose was10Gy. The treatment groups began to use Endostar when the maximal diameter of thetumor grew to0.5cm, intraperitoneal injection once a day, drug concentration was20mg/kg,14days of continuous use, the control group received the same normalsaline. Observed the general condition in nude mice, the tumor volume was measuredevery other day,and calculated the sensitizing coefficient. The tumor tissue wasanalyzed by immunohistochemistry, vascular density was detected by CD34. What’smore, the tumor tissues were assessed by Werstern blot analysis, and detected theexpression of VEGF and PTEN among the groups.Results: The general state of health in nude mice, compared with the controlgroup, the appetite of nude mice in the10Gy group and combined treatment group innude mice eating slightly reduced, that of the Endostar group was normal. Nude miceskin ulceration, the skin ulceration of the blank control group were more than anyother groups. From the growth curve of tumor, compared with the control group, thetumor growth of the Endostar group,10Gy group and combined treatment grouptumor growth were inhibited to some different extent, especially in the combinedtreatment group. To calculate the doubling time in each group, we found that thecombined treatment group was15days which was significantly longer than the others.Sensitizing coefficient EF was2>1, which illustrated recombinant humanendostatin could increased the sensitivity of radiation therapy for lung adenocar-cinoma. By immunohistochemistry assay the tumor tissue of vascular endothelial cells in the surface of CD34in control group and Endostar group in tumor tissue ofvascular endothelial cells in the surface of CD34, the results showed that CD34haddifferent levels of expression in transplanted tumor of the two groups. Themicrovessel density, MVD of the Endostar group and control group were3.2±0.84and7.0±3.5, respectively, on the seventh day, which were significant difference(p=0.024＜0.05), the MVD was obvious difference between the control group5.3±1.5and the Endostar group3.0±0on the fourteenth day (p=0.037＜0.05). On theforty-eighth day, the MVD of the control group was3.0±0, Endostar group MVD was4.2±1.3(p>0.05). It was thus clear that the tumor MVD of the using Endostar groupdecreased after administration. And after stopping the treatment, the MVD of theusing Endostar group increased gradually close to the blank group. The expression ofVEGF and PTEN witch was detected by Western blot on the Fourteenth day showedthat the expression of VEGF in the Endostar group was down-regulation comparedwith that in the control group in the same amount actin relative of cases, but theexpression of VEGF in the10Gy group compared with that in the control group wassignificantly up-regulated; the expression of VEGF in the combined treatment groupcompared with that in the control group was significantly down-regulated. But theexpression of PTEN protein in the control group compared with that in the othergroups was not significant meaning.Conclusions: Recombinant human endostatin could effectively inhibit the tumormicrovessel density, inhibit angiogenesis, and inhibit the growth of tumor, and hadobvious radiosensitization on lung adenocarcinoma. And could decrease the vasculardensity of transplanted tumor by obviously downing the expression of VEGF, toachieve the radiosensitizing effect. |
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