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Gastric cancer is a common malignant tumor of the gastrointestinal tract， with the pathogenesis remains to be fully elucidated. Although surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy have demonstrated obvious clinical efficacy in the treatment of gastric cancer， the patients suffer from complications and adverse effects. Basic experiments and clinical studies have proved that Chinese medicine can treat gastric cancer in a multi-component and multi-target manner， the mechanisms of which remain to be deciphered. Therefore， the mechanism of Chinese medicine against gastric cancer needs to be unveiled by network pharmacology and tools of molecular biology. According to Chinese medicine， the occurrence of gastric cancer is mainly attributed to liver Qi stagnation， phlegm stasis and Qi stagnation， body fluid deficiency and heat accumulation， deficiency of healthy Qi， and cancer toxin accumulation. According to the available literature， herbal compound formulas such as Sancao Tiaowei decoction， Xiaojianzhong decoction， and Yiqi Huayu Jiedu decoction focus on tonifying， clearing heat， and detoxifying， while herbal active components are mainly insecticidal， heat-clearing， blood-activating， stasis-removing， and Qi-regulating drugs. The therapeutic effects of these Chinese medicines are consistent with the etiology and pathogenesis of gastric cancer. It has been demonstrated that Chinese medicines play a role in promoting apoptosis and autophagy， blocking cell cycle， and reversing cellular drug resistance to treat gastric cancer by regulating phosphatidylinositol-3 kinase/protein kinase B （PI3K/Akt）， mitogen-activated protein kinase （MAPK）， nuclear factor-kappa B （NF-κB）， transforming growth factor-β （TGF-β）/Smad， Wnt/β-catenin， and Hedgehog signaling pathways， while there is a lack of systematic understanding. By systematically summarizing the signaling pathways related to the regulation of gastric cancer by Chinese medicine， this study aims to clarify the molecular mechanisms of Chinese medicine against the development， invasion， and metastasis of gastric cancer， with a view to providing new targets， perspectives， and ideas for the treatment of gastric cancer and promoting the modernization of traditional Chinese medicine.
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Aim To investigate the effects of ursolic acid from loquat leaves on proliferation inhibition and expression of PPAR-γ 、TGF-β1 in rat hepatic stellate cells, so as to explore the mechanism of anti-hepatic fibrosis of UA.Methods HSC-T6 cells were randomly divided into blank group, rosiglitazone control group, the low, medium and high concentration of UA group to detect the cell proliferation inhibition by CCK-8 after 24,48,72 h.The content of type collagen Ⅰ in cell culture supernatant of each group was examined by ELISA.The expression of PPAR-γ mRNA, TGF-β1 mRNA in HSC-T6 cells exposured were examined by real-time quantitative PCR.Effects on HSC-T6 PPAR-γ and TGF-β1 protein from each group were detected by immunocytochemical method.Results CCK-8 results showed that the inhibitory rate of UA on cell proliferation increased with the prolongation of drug action time(P<0.01).ELISA results showed that with the increase of the concentration of UA, the content of type Ⅰ collagen content decreased(P<0.01).Real-time PCR results showed that with the increase of the concentration of UA, and the expression of PPAR-γ mRNA increased, the expression of TGF-β1 mRNA decreased(P<0.01).The results of immunocytochemistry showed that the expression of PPAR-γ protein was increased, and the expression of TGF-β1 protein was decreased with the increase of the concentration of UA(P<0.01).All effects mentioned above were dose-dependent.Moreover, the effects in the high concentration groups were stronger than those in control group.Conclusion UA can inhibit the proliferation of HSC-T6 cells, Which may be associated with the up-regulation of PPAR-γ expression and the down-regulation of TGF-β1 expression.
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Objective To observe the prevention and treatment of the total flavonoids from Litchi chinensis Sonn( TFL) on hepatic fibrosis induced by dimethylnitrosamine(DMN)in rats, and to explore its mechanism. Methods Ninety SD rats were randomly divided into six groups, normal control group, model control group, colchicine group, high-, medium- and low-dose TFL group(n=15).Expect for normal control group, the other groups were given intraperitoneal injection of 2 mL.kg-1 of 5% dimethylnitrosamine for 4 weeks as the model group. The rats in the normal control group and model control group were given 5 mL.kg-1of 0.9% sodium chloride solution, colchicine group was treated with 0.1 mg.kg-1 colchicine.High-, medium-and low-dose TFL groups were given 200, 100 and 50 mg.kg-1 of TFL.The rats were sacrificed and the livers were harvested and stained with HE and Masson staining to observe pathological changes and liver fibrosis in the same part 6 weeks after all the medicine was given to the rats each day. Immunohistochemistry and Western blotting were used to detect the expression of the transforming growth factor β-Ⅰ/type Ⅱ receptor ( TβRⅠ/Ⅱ) , collagen Ⅰ( Col Ⅰ) and Ⅲ collagen ( Col Ⅲ) . Results Compared with the normal control group, the semiquantitative score of liver fiber and the protein expression of TβRⅠ, TβRⅡ, ColⅠ and Col Ⅲ in the model control group were significantly increased(P<0.01).Compared with the model control group, the protein expression levels of TβR, TβRⅡ, ColⅠand ColⅢwere significantly decreased( P<0.01) in the high-,medium-and low-dose TFL group.The semiquantitative score of liver fiber was significantly decreased( P<0.01) with a dose-effect relationship. Conclusion TFL can inhibit formation of DMN-induced liver fibrosis in rats, which may be related with reduction of expression of TβRⅠ/Ⅱ of hepatic fibrosis promoting factor TGF-β1 , inhibition of the activation and increase of hepatic stellate cells, reduction of the collagen content.
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Objective To investigate effects of total flavonoids of litchi (TFL) on the proliferation of rat hepatic stellate cells (HSC-T6) in comparison with western medicine rosiglitazone, and to explore the mechanism of anti hepatic fibrosis of TFL. Methods Effect of TFL on proliferation of HSC-T6 was examined by MTT. The expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) mRNA, connective tissue growth factor (CTGF) mRNA in HSC-T6 cells exposured were examined by real-time quantitative PCR. Effects on HSC-T6 CTGF protein from TFL and rosiglitazone were detected by Western bloting. Results The expression of PPAR-γ mRNA was upregulated and the expression of CTGF mRNA and protein was downregulated after exposure to TFL and rosiglitazone for 72 hours. And the effect of TFL increased with the increase of concentration. Conclusion TFL can inhibit the proliferation of HSC-T6 and antagonizing liver fibrosis. This mechanism may be associated with the upregulation of PPAR-γ expression and the downregulation of CTGF expression.