Experimental Study Of Modified Qige San In Inhibiting Esophageal Carcinoma Metastasis

Objectives: To explore the mechanism of modified Qigesan on inhibiting lung metastasis of esophageal carcinoma in nude mice by observing the number of lung metastasis nodules in nude mice,inhibition of tumor and lung metastasis in 615 mice,and the expression of E-cadherin,keratin 8,snail,Cx43,and WNT2 proteins in tumor tissue.Methods:1 in this study we established nude mice model of esophageal lung metastasis with esophageal cancer cells KYSE150,divided them randomly into normal saline group,capecitabine group and modified Qigesan group,nude mices' weight were weighed in every other day,and the lung metastasis of nude mice was observed by using vivo imaging system.We also established 615 mice model of esophageal lung metastasis with pregastric cancer cells MFC,injected the cancer cells in the right scapula subcutaneous,then divided them randomly into normal saline group,capecitabine group and modified Qigesan group.From the third day after injection,dosing began to intervene,the long and short diameters of tumor were measured every three days.Tumor and lung tissue were dissected after sacrificed the mice.2 Counted the lung metastasis nodules of nude mice and 615 mice in each group,and performed the microscopic examination of lung metastases by HE staining.3 Draw the body weight curve of nude mice in each group and observe each group's life quality.4 Western bolt method was used to detect the expression of E-cadherin,keratin 8,Cx43,snail and WNT2 in pulmonary metastasis nodules.Results:1.The bioluminescence of tumor cells was detected by animal biopsy system 12 weeks after inoculation,suggesting spontaneous lung metastases.Among them,the photon intensity of modified Qigesan group and Capecitabine group was lower than that of saline group.2.The lungs of nude mice showed gray-white lung metastasis nodules,of which the number of lung nodules in modified Qigesan group and capecitabine group were less than those in negative control group,the difference was statistically significant(P<0.05).3.The body weight and initial weight percentage of nude mice in each group showed significant body weight reduction in capecitabine group,while modified Qigefang group weight loss was not obvious.4.We established succefully the 615 mouse subcutaneous transplant tumor metastasis model.the number of lung nodules and tumor diameter in modified Qigesan group and capecitabine group were less than those in negative control group,the difference was statistically significant(P<0.05),while there was no statistical difference between modified Qigesan group and capecitabine group.5.Under the microscope,we observed HE staining of the metastatic nodules in each group,which was poorly differentiated squamous cell carcinoma.Cell atypia was obvious,the shape was diverse,the nucleus was bigger than normal cells,Nuclei darker,and coarse grainy.6.Western blot results showed that the expressions of E-cadherin,keratin8 and Cx43 in Qigefang group and Capecitabine group were significantly increased(P <0.05),and the expressions of snail and WNT2 protein were significantly decreased(P <0.05).Conclusion:1.Modified Qigesan can inhibit the lung metastasis of esophageal cancer in nude mice and improve the quality of life in nude mice.2.Modified Qige San can inhibit the tumor growth and lung metastasis of tumor-bearing mice.3.Modified Qige San can enhance the expression of E-cadherin,keratin 8,Cx43 and reduce the expression of snail and WNT2 in esophageal cancer cells.