Xu Jingyu, Shen Wei, Pei Bei, Wang Xiaowei, Sun Dazhi, Li Yongjin, Xiu LiJuan, Liu Xuan, Lu Ye, Zhang Xuan, Yue XiaoQiang
Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Changjiang Road Community Health Service Center, NO. 639, Tonghe Road, Zhangmiao Street, Baoshan Qv, Shanghai, 200431, China.
Biomed Pharmacother. 2018 Dec;108:95-102. doi: 10.1016/j.biopha.2018.09.012. Epub 2018 Sep 12.
In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.
近年来,中医在胃癌的预后中发挥了重要作用。胃癌癌前病变(PLGC)是一类与胃癌密切相关的疾病,在致癌因素作用下,其胃黏膜病理变化在正常胃黏膜细胞向胃癌细胞的转变过程中起关键作用。在当前实验中,我们在PLGC大鼠动物模型以及用1-甲基-3-硝基-1-亚硝基胍(MNNG)诱导的上皮-间质转化的GES-1细胞中,探究了中药(消痰和胃汤)与胃癌之间的关系。PLGC大鼠模型显示胃黏膜显著恶化,体重增长缓慢,胃黏膜出现更多非典型增生。与正常GES-1细胞相比,MNNG诱导的GES-1细胞中上皮-间质转化(EMT)相关蛋白有很大变化。这些细胞具有恶性细胞的特征,包括增殖、侵袭和转移能力。我们的研究发现,消痰和胃汤可通过提高促凋亡蛋白如Bax和caspase-3的水平、降低抗凋亡蛋白Bcl-2的水平来抑制细胞增殖并增加细胞凋亡,同时将细胞阻滞在G0/G1期。此外,消痰和胃汤可抑制核因子κB(NF-κB)活性,并抑制其从细胞质转移到细胞核。然而,当我们用NF-κB激活剂佛波酯(PMA)孵育时,消痰和胃汤的作用被逆转。这些结果表明,消痰和胃汤可作为治疗胃癌前病变的一种方法,可能为胃癌及胃癌前病变的临床治疗提供理论依据。
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