Cryptotanshinone Inhibits Esophageal Squamous-cell Carcinoma In Vitro And In Vivo Through The Suppression Of STAT3 Activation

Esophageal cancer is a common malignant tumor of the digestive tract.In recent years,the incidence of esophageal cancer has increased year by year.China is one of the countries with the highest incidence of esophageal cancer in the world.There are two types of histology in esophageal cancer,namely esophageal squamous cell carcinoma and esophageal adenocarcinoma.Esophageal cancer has become a major killer of human health because of its high mortality rate.Therefore,it is imperative to find an effective medicine.Cryptotanshinone has many pharmacological effects such as antibacterial,anti-inflammatory,anti-oxidation and treatment of cardiovascular diseases.Studies have shown that cryptotanshinone inhibit the expression of STAT3 in cancer cells,and STAT3 is abnormal in esophageal cancer cells and tissues.Therefore,our research is mean to study about the molecular mechanism of cryptotanshinone against esophageal cancer.Provide a theoretical basis for clinical treatment of esophageal cancer.In our study,MTT assay was used to detect the inhibitory effect of different concentrations of cryptotanshinone on the proliferation of esophageal cancer cells,and the IC50 values at different administration times.The basic expression of STAT3-related proteins in esophageal cancer cells were detected by Western blotting.The effect of cryptotanshinone on apoptosis of esophageal cancer cells was detected by flow cytometry using Annexin-FITC/PI double staining.The effect of cryptotanshinone on the genes and expression of STAT3 related proteins downstream in esophageal cancer cells by Western blotting.The effect of cryptotanshinone on the migration ability of esophageal cancer cells was evaluated by scratch test.Use xenograft tumor experiment detect tumor growth in nude mice and the anti-tumor effect of cryptotanshinone in vivo.The expression of Ki-67 in tumor tissues were detected by immunohistochemical staining.In vitro experiments showed that cryptotanshinone can inhibit the proliferation of esophageal cancer cells,and the IC50 value decreases with the prolongation of administration time.The expression of STAT3 and p-STAT3 protein is abnormal in esophageal cancer cells,and cryptotanshinone inhibit its activation.Cryptotanshinone can promote apoptosis of esophageal cancer cells,and inhibit the metastasis of esophageal cancer cells.In vivo experiments showed that cryptotanshinone inhibit the growth of xenografts in nude mice,and has no significant effect on the body weight of nude mice.Cryptotanshinone can inhibit the expression of STAT3 and its related proteins in nude mice and reduce the positive rate of KI-67.In summary,cryptotanshinone can inhibit the proliferation of esophageal cancer cells,promote the apoptosis of esophageal cancer cells,and inhibit tumor growth in vivo by inhibiting the activation of JAK2/STAT3 signaling pathway in esophageal cancer cells,and treating esculent in the body.To provide a theoretical basis for the use of cryptotanshinone as a new clinical drug for the treatment of esophageal cancer.