Effect and Mechanism of Modified Lichong Decoction on Inhibiting Proliferation and Inducing Apoptosis in AGS Gastric Cancer Cells.

Abstract

BACKGROUND: Lichong decoction, a classic Chinese herbal formula, has been applied to treat gynecological diseases and abdominal masses. According to pathogenesis of gastric cancer, we add some Chinese herbs to form the formula of modified Lichong decoction (MLCD) for treatment gastric carcinoma. AIM: To investigate the effect of MLCD on inhibiting proliferation and inducing apoptosis, and to explore its molecular mechanisms through metabolomics and pharmacological validation in AGS gastric cancer cells. METHODS: The CCK-8 assay, bromodeoxyuridine (BrdU) staining, morphological observation, DNA gel electrophoresis, and Annexin V-FITC/PI staining were employed to evaluate the pharmacological effect of MLCD. The potential molecular mechanism of MLCD was evaluated by metabolomics and pharmacological verification. RESULTS: The pharmacological effects showed that MLCD could inhibit proliferation, induce apoptosis, and affect the expression of apoptosis-related genes and proteins (Bcl-2, Bim, Bax, Fas, and FasL) in AGS cells. The metabolomics results verified that multiple signalling/metabolic pathways, including the PI3k/Akt signalling pathway, were involved in MLCD-treated AGS cells. Subsequently, we conducted a pharmacological verification by combining with LY294002. The results showed that MLCD could reduce the protein expression levels of p-Akt and p-FoxO3a and enhance the nuclear translocation of FoxO3a. All results revealed that combining with LY294002 had more significant pharmacological effects. Meanwhile, the synthetical results of previous network pharmacology verified the related targets of MLCD for anti-gastric cancer. The results showed that MLCD could reduce the gene and protein expression of P53, P21, LKB1, and AMPK in AGS cells. CONCLUSION: MLCD could suppress proliferation and induce apoptosis in AGS cells, which may involve the mitochondrial apoptotic pathway, death receptor pathway, P53/P21 pathway, LKB1/AMPK pathway, and PI3k/Akt pathway.

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