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Esophageal squamous cell carcinoma （ESCC）， the predominant histological strain of esophageal cancer in China， is complex in pathogenesis and may be associated with mutations in several genes and dysregulation of the mitogen-activated protein kinase （MAPK） pathway， the phosphatidylinositol 3-kinase （PI3K） pathway， etc. MAPK signaling pathway can be activated by growth factors， proto-oncogenes， and oxidative stress， thus participating in biological functions such as cell proliferation， differentiation， migration， and apoptosis. More evidence shows that the MAPK signaling pathway plays an important role in the occurrence and development of ESCC and is expected to become an effective target for the treatment of ESCC. The classical MAPK family consists of extracellular signal-regulated kinases 1/2 （ERK1/2）， c-Jun N-terminal kinases 1/2/3 （JNK1/2/3）， p38 α/β/γ/δ， and extracellular signal-regulated kinase 5 （ERK5）. Each pathway consists of three cascade sequentially phosphorylated and activated protein kinase systems. The activation of the ERK1/2 pathway is related to the proliferation， migration， drug resistance， and apoptosis inhibition of ESCC. JNK， p38， and ERK5 pathways seem to show bidirectional regulation， and there is signal integration between MAPK internal pathways. Chemotherapeutic drugs for esophageal cancer often have side effects and are prone to drug resistance， so it has become a new idea to find effective and low-toxic drug alternatives. Studies have found that flavonoids， terpenoids， alkaloids， saponins， phenols， and other active ingredients in Chinese medicine can play an anti-ESCC effect by targeting the MAPK pathway， which is mainly reflected in inhibiting proliferation， migration， and invasion， inducing cycle arrest， promoting apoptosis， reversing drug resistance， etc. Therefore， this paper reviewed the regulatory role of the MAPK signaling pathway in ESCC and the research progress in active ingredients of Chinese medicine in regulating MAPK pathway against ESCC to provide references for the mechanism research and new drug development of Chinese medicine in the prevention and treatment of esophageal cancer.
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Esophageal cancer ranks the seventh and sixth in morbidity and mortality among the malignant tumors， respectively. In traditional Chinese medicine， toxic medicinals are commonly used to enhance the efficacy on esophageal cancer. In recent years， as natural drugs have become the focus of research on anti-tumor drugs， toxic Chinese medicinals have received wide attention. It has been found that a variety of toxic Chinese medicinals have significant anti-esophageal cancer effect. In this study， articles on the treatment of esophageal cancer were retrieved from SinoMed， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP， and the toxic Chinese medicinals in the articles were summarized. It was found that the toxic Paridis Rhizoma， Gekko， Cremastrae Pseudobulbus Pleiones Pseudobulbus， Scolopendra， Hirudo， Sophorae Tonkinesis Radix et Rhizoma， Scorpio， and Bufonis Corium were mainly used for the treatment of this cancer. They can be classified into the heat-clearing and toxin-removing medicinals， toxin-counteracting medicinals， phlegm-resolving medicinals， and blood-activating and stasis-resolving medicinals. Most of them were pungent （19，52.78%） or bitter （17，47.22%）. The majority had the meridian tropism toward liver （25， 69.44%）， spleen （13， 36.11%）， and lung （12， 33.33%）. According to the research on the above commonly used toxic Chinese medicinals， most of them have anti-tumor effect and some have been reported to have anti-esophageal cancer effect. The mechanism is mainly the inhibition of proliferation. To be specific， they exert the anti-cancer effect by suppressing the proliferation， migration， and differentiation of cancer cells， inducing cell cycle arrest， and activating B-cell lymphoma/leukemia-2 （Bcl-2）-associated X protein （Bax）/Bcl-2/Caspase signaling pathway to induce apoptosis. In this paper， the commonly used toxic Chinese medicinals for the treatment of esophageal cancer were statistically analyzed， and the mechanisms were summarized， in order to provide a reference for the clinical rational use of toxic Chinese medicinals and the research on the mechanisms for their efficacy.
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OBJECTIVE：To study the effects and mechanism of water extract and ethanol extract of Muskmelon Pedicel on the proliferation，migration and cloning formation of esophageal carcinoma TE- 1 and EC- 1 cells. METHODS ：TE-1 and EC- 1 cells were cultured in vitro ，and were treated with 0，1.562 5，3.125，6.25，12.5，25，50，100，200 μg/mL of water extract and ethanol extract of Muskmelon Pedicel （calulated by extract powder ）. MTT assay was used to detect the growth inhibitory rate of TE- 1 and EC-1 cells，and calculate IC 50 of them. TE- 1 and EC- 1 cells were divided into TE- 1/EC-1 blank group ，TE-1/EC-1 Muskmelon Pedicel water extract group （IC50 as drug concentration ），and TE- 1/EC-1 Muskmelon Pedicel ethanol extract group （IC50 as drug concentration）. The proliferation and migration of cells in each group were detected by real-time unlabeled cell analysis （RTCA）， and cell proliferation and migration curves were drawn. The morphological changes of cells were observed under microscope ；soft agarose colony forming test was used to analyze the change of colony forming ability of cells in each group ，and the colony forming rate was calculated ；cell cycle and apoptosis rate of cells in each group were detected by flow cytometry ；Western blotting assay was used to detect the relative expression of EGFR and PKC -α in cells in each group. RESULTS ：IC50 of water extract of Muskmelon Pedicel were 49.24，76.38 μg/mL respectively for TE-1 and EC- 1 cells. Those of ethanol extract of Muskmelon Pedicel were 9.08，14.53 μ g/mL respectively for TE-1 and EC- 1 cells. The inhibition effect of water extract and ethanol extract of Muskmelon Pedicel on the cell proliferation were within 30 h. Δ 基金项目：河南省自然科学基金资助项目（No.162300410185） ＊博士研究生。研究方向：肿瘤中医方证。电话：0371-65676778。 The inhibition effect of water extract and ethanol extract of E-mail：zixiangning88@126.com Muskmelon Pedicel on the cell migration were within 60 h. # 通信作者 ：教授，博士生导师 ，博士。研究方向 ：肿瘤中医方 Compared with TE- 1/EC-1 blank group ，the number of cells 证。电话：0371-65676778。E-mail：sifc2000@hotmail.com was decreased significantly in administration groups ， the ·314· China Pharmacy 2020Vol. 31 No. 3 中国药房 2020年第31卷第3期 structure of cell were sloop ，the cell structure was loose ，and most of the cell contour disappeared and became round. The formation rate of cell clone was decreased significantly （P＜0.01）. The percentage of G 2 phase cells increased significantly （P＜ 0.01），while that of G 1 and S phase cells decreased significantly （P＜0.05）. The apoptotic rate of cells increased significantly in early and late stage （P＜0.05）. Relative protein expression of EGFR and PKC- α were decreased significantly （P＜0.01）. Compared with TE- 1/EC-1 Muskmelon Pedicel water extract group ，formation rate of cell clone was decreased significantly in TE- 1/EC-1 Muskmelon Pedicel ethanol extract group （P＜0.05）；cell was increased significantly at G 2 phase（P＜0.05）；relative protein expression of EGFR and PKC- α were decreased significantly （P＜0.01）. The apoptotic rate of cells in early and late stage in TE- 1 Muskmelon Pedicel ethanol extract group was decreased significantly （P＜0.05），the apoptotic rate of cells in early and late stage in EC- 1 Muskmelon Pedicel ethanol extract group was increased significantly （P＜0.05）. CONCLUSIONS ：Water extract and ethanol extract of Muskmelon Pedicel could influence the proliferation ，migration and clone formation ability of TE- 1 and EC- 1 cell，promote cell apoptosis ，the mechanism of which may be associated with the down-regulation of EGFR and PKC-α protein.
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Objective To probe the regulation of TCM treatment for essential hypertension by analyzing the frequency of herbs usd in the literature of hypertension TCM treatment included in CNKI from 1979 to 2009 with a view to provide a reference for the clinical treatment and research.Methods The herbs meeting the inclusion criteria in the selected literature was recorded by using Excel table,and analyzed by using SPSS13.0 statistical software.Results Of the 301 herb medicine,the tonics,heat-clearing,calming liver wind,promoting blood circulation and removing blood stasis,removing dampness and promoting diuresis,diaphoretics totally accounted for 79.16%.The attributive channel of these herbs involved in 12 viscera,in which liver meridian,kidney meridian,spleen meridian,heart meridian accounted for 66.97%.All herbs involved in 7 kinds of herbal flavors,and total appearance frequency of the 7 flavors was 12584,in which sweetish,bitterness,pungent herbs accounted for 82.99%.Conclusion Efficacy,property flavors and attributive channel of herb medicine used for essential hypertension are closely related to the pathogen and pathogenesis.These herbal medication regularity provides a reference for the current syndrome differentiation and treatment of essential hypertension.
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To discuss the effects of medical policies and social background in Song Jin Juan dynasties on TCM theoretic development and innovation. To summarize the achievement in the anatomy,classical writings,etiology and pathogenesis theories,theory of visceral manifestation,meridian theory and their guiding roles in the clinic practices.At last,we analyze the influential factors of development of the basic theory of TCM,it provides some traces for the further study on basic theory of TCM.
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regulating qi group.The difference in tumor inhibitory rate of whole formula group and nourishing yin group was significant(P