Effect of Qigesan on Proliferation， Apoptosis and miR-133a/Akt/mTOR Signaling Pathway of Esophageal Cancer EC9706 Cells / 中国实验方剂学杂志

Objective:To observe the effect of Qigesan on the proliferation and apoptosis of the human esophageal cancer cell EC9706， and the effect on miR-133a/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway. Method:The effective constituent of Qigesan was extracted by ethyl acetate. Thiazolyl blue tetrazolium bromide（MTT） colorimetric assay was used to determine the dosage of Qigesan on cells and to detect the effect of Qigesan on the proliferation of EC9706 cells. The effect of Qigesan on apoptosis of EC9706 cells was detected by flow cytometry. The effect of Qigesan on miR-133a and insulin-like growth factor 1 receptor（IGF-1R） mRNA expression was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） . The protein expression of Akt and mTOR in EC9706 cells was detected by Western blot. Result:Qigesan can inhibit the proliferation of EC9706 cells in a dose-dependent manner（<italic>P</italic><0.01）. Inhibitory concentrations 30% inhibition concentration（IC₃₀） 40 mg·L^-1 and median inhibition concentration（IC₅₀） 80 mg·L^-1 were selected for follow-up experiments. Compared with the blank group， both the inhibitor group and the combination drug group can inhibit the proliferation of EC9706 cells （<italic>P</italic><0.01）. The inhibitor at 0.25 μmol·L^-1 was selected for subsequent experiments. Compared with the blank group， Qigesan 80 mg·L^-1 dose group could significantly promote the late apoptosis rate and total apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， and the 40 mg·L^-1 dose group could significantly promote the late apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， which shows synergistic effect after concomitant use with Akt/mTOR inhibitor（<italic>P</italic><0.05）. Compared with the blank control group， each group can effectively increase expression of miR-133a（<italic>P</italic><0.05）. The combination of inhibitor and traditional Chinese medicine（TCM） has obvious promotion effect. Compared with blank control group， the expressions of Akt and mTOR were significantly decreased in each group（<italic>P</italic><0.05）. Compared with single medication， the expressions of Akt and mTOR were decreased in combination of inhibitor and TCM group. Conclusion:Qigesan can inhibit the growth of EC9706 cells and promote apoptosis， and its inhibitory mechanism may be related to the Akt/mTOR signaling pathway by regulating the expression of miR-133a.

Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Esophageal cancer is one of the malignant tumors with a high morbidity and mortality in China. According to China's latest cancer report released by the National Cancer Center in 2019, the number of people suffering from esophageal cancer reached 246 000 in 2015, and the death toll reached 188 000. How to effectively treat esophageal cancer and improve the survival rate of patients is one of the most urgent problems in the field of medicine. Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most important signaling pathway for regulating cell survival, differentiation and apoptosis in the body. It also plays an important role in the occurrence and mechanism of various cancers. Recent studies have shown that the activation of PI3K/Akt signaling pathway is an important factor in regulating proliferation, apoptosis, cycle arrest, migration and invasion of esophageal cancer cells. The long-term clinical observation found that traditional Chinese medicine has a stable effect in the treatment of esophageal cancer and little side effects, especially in improving the quality of life of cancer patients and prolonging the survival period of patients. At present, it is a research hotspot to intervene this signal pathway with traditional Chinese medicine in the treatment of esophageal cancer, so as to explore its mechanism of action on esophageal cancer. This paper focused on literatures in CNKI and PubMed databases from 2009 to 2019, with PI3K/Akt signaling pathway, esophageal cancer and miRNA as the key words. A total of 226 literatures were retrieved, and 61 literatures relating to traditional Chinese medicine, esophageal cancer, miRNA and PI3K/Akt signaling pathway were sorted out and summarized. This paper reviewed the mechanism of PI3K/Akt signaling pathway in esophageal cancer, the relationship between miRNA and PI3K/Akt signaling pathway and esophageal cancer, and how traditional Chinese medicine can regulate the expressions of relevant proteins in PI3K/Akt signaling pathway to inhibit cell proliferation, affect cell growth cycle, induce cell apoptosis, inducing cell autophagy, inhibit tumor invasion and metastasis, inhibit angiogenesis. Finally, it can improve esophageal cancer to provide theoretical basis and scientific basis for the treatment of esophageal cancer with traditional Chinese medicine.