Effect Of Ivermectin Combined With Tripterine On Inhibiting The Proliferation Of Esophageal Carcinoma Cells

[Background] The Esophageal squamous cell carcinoma(ESCC)is one of the malignant tumors with high incidence in China,which is considered as an aggressive cancer due to its poor prognosis and high mortality rate.Accumulation of evidence shown that most patients were diagnosed with locally advanced or metastatic ESCC which is unable to undergo radical surgical resection,approximately 80% of these patients were undergone radiotherapy and chemotherapy,or combination of these.However,there are few drug candidates with long-term efficacy in the treatment of ESCC,which suggests that it is urgent to identify new drugs to improve systemic therapy for ESCC patients.Ivermectin(IVM)is a polycyclic lactone antiparasitic drug produced by Streptomyces.It is found to have good antitumor activity in melanoma,breast cancer,leukemia,glioma,etc.This also suggests that we should take measures to reduce the adverse reactions of this drug so as to better play its anti-tumor activity.Tripterygium wilfordii red element(Celastrol,Cel)is a kind of pentacyclic triterpene compounds with high biological activity,the study found that it's in the induction of prostate cancer,melanoma,glioma and so on many kinds of cancer cells apoptosis and inhibit the growth of tumor cell proliferation effect is remarkable,our previous experiments have found that tripterygium wilfordii red element through the mitochondrial function mechanisms such as esophageal cancer cell proliferation inhibition,at the same time,the Chinese traditional medicine side effect,small suggesting we can make use of the drugs for combination therapy.In recent years,studies have found that the combined application of drugs can give full play to the biological activity of the drug,while reducing the side effects of the drug,and has a better effect on tumor treatment.Therefore,exploring the role of drug combination is of great significance for the treatment of esophageal cancer.[Objective ] To investigate the inhibitory effect of ivermectin combined with tripterine and the molecular mechanism of ivermectin on the proliferation of esophageal cancer cells.[Methods]1.MTT method,clone formation experiment,Ed U experiment,nude mouse transplantation experiment and immunohistochemical staining were used to detect the inhibitory effect of ivermectin on the proliferation of esophageal cancer cells.2.MTT method,morphological detection and clone formation experiment were used to detect the inhibitory effect of ivermectin combined with Celastrol on esophageal cancer cells.3.Ivermectin inhibits the proliferation of esophageal cancer cells by inducing apoptosis,and is closely related to mitochondrial dysfunction and ROS/NF-?B pathway.[Results]1.Ivermectin can significantly inhibit the proliferation of esophageal cancer cells and has a certain dose dependence.2.The inhibition of tripterine and ivermectin combined with tripterine on the proliferation of esophageal carcinoma cells was detected by MTT assay,morphological detection and clone formation experiment.3.Ivermectin could inhibit the proliferation of esophageal cancer cells by inducing apoptosis.Apoptosis induced by ivermectin was associated with mitochondrial function.Ivermectin induced apoptosis of esophageal cancer cells through the ROS/NF-?B pathway.[Conclusion]1.Ivermectin combined with Celastrol can significantly inhibit the proliferation of esophageal cancer cells in vivo and in vivo.2.Ivermectin induces apoptosis of esophageal cancer cells through the ROS/NF-?B pathway.