Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action. Methods:The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches.Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment.Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.
Background Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear. Methods The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α. Results The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC 50 ; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC 50 . The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α. Conclusion MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest.
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