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Study of the Effect of Endostar Injected into Tumor on Mice Lewis Lung Cancer

Author: WangLiFang
Tutor: WangBaoCheng
School: Taishan Medical College
Course: Oncology
Keywords: Recombinant human vascular endothelial the inhibin ( endostar , Endostar) Lweis lung cancer Tumor angiogenesis VEGF MVD
CLC: R734.2
Type: Master's thesis
Year: 2010
Downloads: 39
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Abstract


Objective To observe the percutaneous intratumoral injection of recombinant human endostatin (Endostar, Endostar) plus cisplatin antitumor effect on mice with Lewis lung carcinoma subcutaneous xenografts and toxicity for clinical intratumoral injection of recombinant human vascular endostatin with chemotherapy drugs associated with the treatment of lung cancer and provide experimental basis. Method. C57BL / 6 mice with Lewis lung carcinoma (LLC) right upper extremity axillary subcutaneous xenograft model. 2 experimental groups were inoculated according to body weight were randomly divided into five groups, each group of 10. Long to be transplanted tumor volume to about 400mm3 given drug intervention. Saline group (NS), saline daily intraperitoneal injection of 0.2ml of 10 days; cisplatin group (DDP group), cisplatin 2mg / (kg · d) daily intraperitoneal injection of 7 days; intratumoral injection (kg · d) daily intraperitoneal injection of a total of seven days, at the same time the United endostar 5 mg / (kg · d) by intraperitoneal injection daily, for 10 days; cisplatin combined with intratumoral injection Endostar group [DDP Endo (it) cisplatin 2mg / (kgd) daily intraperitoneal injection of a total of seven days, while local Endostar 5mg / (kg · d) daily intratumoral injection of 10 days. 3. General condition of mice observed the mice were observed for reaction daily, feeding, drinking, activity status generally. 4 the change in tumor volume, drawing tumor growth curve of the tumors were measured with a vernier caliper maximum diameter (L) and perpendicular to the wide diameter (W), measured every 3 days 1, tumor volume V = LW2 / 2, to draw each group transplanted tumor growth curve (0-11 d). Measuring the tumor mass, the inhibitory rate was calculated. Histopathological techniques, to observe tumor tissue structure and lung metastasis, the immunohistochemical techniques observe the transplanted tumor microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. The enzyme-labeled immunosorbent assay (ELISA) detection of mouse plasma VEGF concentration. . 5 days after inoculation visible tumor, modeling success. Mice generally medication NS group, the tumor-bearing mice with transplanted tumor nodules gradually grow, eat, drink, and activities than before to reduce; DDP group, DDP Endo (ip) group, DDP Endo (it) mice activity significantly reduced, decreased food intake, but body weight was not significantly reduced. Endo (it) group of mice eating, drinking no significant change compared with the previous normal activities, continued to the end of the experiment. Impact of tumor volume (mm3) of the transplanted tumor volume, quality: each experimental group of mice were subcutaneously transplanted tumor volume with experimental gradual growth, the rapid growth of the NS group volume, and DDP group, Endo (it) group, DDP Endo ( ip) group., DDP Endo (it) group of the slow growth of the tumor volume. The end of the experiment, NS group, DDP group, DDP Endo (ip) group, DDP Endo (it) group the mouse xenograft average volume order 2481.00 ± 392.36 mm3 1124.98 in ± 278.25mm3, 1796.79 ± 256.51 mm3, 734.97 ± 279.77 mm3, 708.35 ± 189.77mm3. Which the NS group and DDP group, Endo (it) group, DDP Endo (ip) group, the DDP Endo (it) group differences were statistically significant (P lt; 0.05); DDP group and Endo (it) group, DDP Endo (ip) group, DDP of Endo (it) group differences were statistically significant; the Endo (it) group and DDP Endo (ip) group, DDP Endo (it) group differences were statistically significant (P lt; 0.05), while the difference between the combination group was not statistically significant (P gt; 0.05), less than DDP Endo (ip) ± group but DDP Endo (it) tumor volume. Tumor Quality (g): NS group 3.86 ± 0.40 and the DDP group 1.49 ± 0.30, the Endo (it) group 2.80 ± 0.17, DDP Endo (ip) group 1.16 ± 0.30, the DDP Endo (it) group, 1.00 ± 0.23. Tumor inhibition rate (%): DDP group 61.44, the Endo (it) group 27.64 DDP Endo (it) group 69.87 DDP Endo (it) group 74.24. Which the NS group and DDP group, Endo (it) group, DDP Endo (ip) group, the DDP Endo (it) group differences were statistically significant (P lt; 0.05); DDP group and Endo (it) group, DDP Endo (ip) group, DDP of Endo (it) group differences were statistically significant; the Endo (it) group and DDP Endo (ip) group, DDP Endo (it) group differences were statistically significant (P lt; 0.05), the DDP Endo (ip) group with the DDP Endo (it) comparison between groups was not statistically significant (P gt; 0.05), but DDP Endo (it) group of tumor weight to reduce the most obvious, the inhibition rate of 74.24%. Transplanted tumor microvessel density CD34 as a marker of vascular endothelial cells, vascular endothelial cell cytoplasm was stained brown. NS group, DDP group, Endo (it) group, DDP Endo (ip) group, DDP Endo (it) The MVD count average 13.8 ± 1.9,11.8 ± 2.4,4.4 ± 1.7,4.2 ± 13,1.8 ± 0.8 . Compared with NS group, each drug intervention group MVD values ??are to reduce; except DDP group the rest Endostar drug intervention in the three groups with the NS group comparison differences are has significantly with sex (P lt; 0.05); DDP group and Endo (it) group, DDP group and DDP Endo (ip) group, the the DDP group with DDP Endo (it) group differences were statistically significant; statistically significant difference between the two combined group, which DDP Endo (it) was significantly lower than group DDP Endo (ip). The transplanted tumor vascular endothelial growth factor expression of VEGF protein in the cytoplasm of the tumor cells, the significant for brown particles. NS group, DDP group, Endo (it) group, DDP Endo (ip) group DDP Endo (it) Group VEGF expression results scores were 6.4 ± 0.9,6.2 ± 0.8,4.4 ± 0.5,4.6 ± 0.5,3.4 ± 1.1 . Compared with NS group, each drug intervention group VEGF protein expression are reduced: In addition to the DDP group the rest Endostar drug intervention in the three groups with the NS group comparison differences are with a significant sex (P lt; 0.05); DDP group and Endo (it ) group, DDP group and DDP Endo (ip) group, the the DDP group with DDP Endo (it) group differences were statistically significant; statistically significant difference between the combined group, which DDP Endo (it) was significantly lower than group DDP Endo (ip). Mouse plasma vascular endothelial growth factor NS group, DDP group, Endo (it) group, DDP Endo (ip) group, DDP Endo (it) plasma VEGF levels are as follows: 115.58 ± 19.92 (pg · ml- 1), 58.97 ± 14.27 (pg · ml-1), 51.90 ± 11.02 (pg · ml-1), 31.10 ± 7.56 (pg · ml-1), 12.63 ± 3.94 (pg · ml-1). Drug intervention group compared with the NS group differences were statistically significant (P lt; 0.01); the DDP group with DDP Endo (ip) group, the the DDP group with DDP Endo (it) group differences were statistically significant ( P lt; 0.05), but the the DDP group with Endo (it) group showed no significant difference (P gt; 0.05). Endo (it) group and DDP Endo (ip) group, Endo (it) groups compared with the DDP Endo (it) group differences were statistically significant (P lt; 0.05); differences between the two combined group also has significant which DDP Endo (it) plasma VEGF levels were significantly lower than the DDP Endo (ip) group (P lt; 0.05). Conclusion 1. Recombinant human vascular endostatin in tumor can be suppressed local injection subcutaneously transplanted tumor growth and metastasis of Lewis lung carcinoma in mice, can increase the anti-tumor effect and no increase in adverse effects compared to systemic administration. 2. Recombinant human vascular endostatin intratumoral local injection may inhibit tumor vascular endothelial growth factor expression, lower serum vascular endothelial growth factor levels, inhibit tumor vascular endothelial cell proliferation, migration, thereby reducing tumor angiogenesis to reduce tumor metastasis. Recombinant human vascular endostatin intratumoral local injection of DDP joint synergistic anti-tumor effect compared with monotherapy group does not increase the adverse reactions of chemotherapy drugs.

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