The Radiosensitization Of Irinotecan In Nude Mice With Ectopic Transplanted Tumor Of Esophageal Carcinoma Cell Lines Eca-109

Objective Esophagus cancer is one of the normal malignant tumors in digestive tract, its incidence of a disease is marked increase in recent years. The present paper evaluated the sensibilization of CPT-11 due to the radiotherapy for esophagus cancer and assessed its curative effect, based on establishing the model of nude mice with xenograft tumor of human esophageal cancer cell lines Eca-109, observing the changing of tumour after CPT-11 combined with radiotherapy, and detection the expression of Ki-67(proliferate related antigen) and Caspase-3 of tumor tissue.Methods Cultivate human esophageal cancer cell lines Eca-109, to establish the model of esophageal carcinoma in nude mice subcutaneously, 36 nude mice were randomly divided into 6groups, 6 in each group:(1) the control group(group A);(2) the CPT- 11 group(group B);(3) simple radiation 15 Gy group(group C);(4)simple radiation 20 Gy group(group D);(5) radiation 15Gy+ CPT-11 group(group E);(6) radiation 20 Gy + CPT- 11 group(group F).Nude mice were tail vein injected with saline in group A; Nude mice were tail vein injected with CPT-11 of 25mg/kg in group B;local tumors were respectively irradiated a single dose of 15 Gy and20 Gy(Gray, Gy) of 6MV linear accelerator in group C and D; Nude mice were tail vein injected with CPT-11 of 25mg/kg, after half an hour, were irradiated a single dose of 15 Gy in group E; Nude mice were tail vein injected with CPT-11 of 25mg/kg, after half an hour,were irradiated a single dose of 20 Gy in group F.Each group tumors growth and changes in the experiment were measured with vernier caliper and drawing tumor growth curves, and measuring of nude mice weight and tumor weight, and calculated tumor inhibition rate and the sensitization enhancement ratio. Synchronously magnetic resonance imaging scans. Used the R2 STAR imaging technology to measure the changes of R2* values of tumor. Observation of 21 days, remove the local tumor.The twenty-first day of the experiment to remove the tumor tissue, HE staining was used to observe the pathological changes of tumor tissue, expression of Ki-67 and Caspase-3 in tumor tissues were detected with immunohistochemical technique.The application of SPSS 20.0software to the test data for statistical analysis.Results The tumor volume in each intervention group were lower than control group, results showed that the inhibition rates of group B, C, D, E, F were 37.7%, 44.9%, 47.7%, 94.8%,95.3%.Group C and group E, group D and group F, the tumor inhibition rate difference was statistically significant(P<0.05); group C and group D, the tumor inhibition rate difference was no statistically significant(P>0.05), and when the radiation dose reaches a certain amount, increase the therapeutic of dose is not obvious effect. Group E sensitization ratio(SER) is 1.68,group F sensitization ratio(SER) is 1.56. Synchronously magnetic resonance imaging scans, and to measure the changes of R2* values of tumor.The qualitative analysis of changes in tumor tissue blood flow,thereby indirectly reflect the degree of inhibition of tumor and the malignant degree of tumor, the result is consistent with theinhibitory rate. HE staining of tumor tissue were observed in each intervention group compared with the control group, the necrosis of tumor cells significantly. Group C and group E,group D and group F,HE staining cell degeneration and necrosis were observed in the difference was statistically significant(P<0.05).Immunohistochemistry technique used to detect the positive rate of Ki-67 expression that sensitive groups were significantly lower than irradiation groups, and the positive rate of Caspase-3 expression that sensitive groups were significantly higher than the irradiation groups.Group C and group E, group D and group F,the positive expression rate difference was statistically significant(P<0.05).Group C and group D, each observation index difference was no statistically significant(P>0.05).Conclusions CPT- 11 has the radiotherapy sensitization effect for transplantation tumor of esophageal carcinoma cell lines Eca-109. The mechanism in addition to the specific inhibition of DNA topoisomerase I and lead to the destruction of DNA damage repaird, may also relate to the inhibition of the expression of Ki-67 and promote the apoptosis of tumor cells. For clinical, the study provides the basis of radiotherapy combined with CPT-11 for the treatment of esophageal carcinoma.