ABSTRACT
Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.
ABSTRACT
ObjectiveTo evaluate the expression of endothelial differentiation gene/lysophosphatidic acid (LPA) receptors (Edg/LPA) and its clinical significance in human pancreatic cancer.MethodsFifty cases of pancreatic cancer and adjacent normal tissues were collected,and Real-time PCR,Western blot and immunohistochemistry was used to determine the expression of Edg-2/LPA1,Edg-4/LPA2 and Edg-7/LPA3 receptors mRNA and protein,and its relationship with clinicopathological parameters was analyzed.Results The expressions of Edg-2/LPA1,Edg-4/LPA2,Edg-7/LPA3 receptor mRNA were (0.142 ± 0.042 ) ％,(0.471 ±0.064)％,(0.231 ±0.043)％ in pancreatic cancer,and the corresponding values were (0.132 ±0.029)％,(0.027 ±0.015)％,(0.163 ±0.046)％ in adjacent normal tissues.The expressions of Edg-4/LPA2 receptor mRNA in pancreatic cancer were significantly lower than that in adjacent normal tissues ( P ＜0.05 ).The expressions of Edg-4/LPA2 receptor protein in pancreatic cancer were significantly lower than that in adjacent normal tissues ( P ＜ 0.05 ).The expressions of three types of Edg /LPA receptor mRNA in pancreatic cancer were parallel to serum CA19-9 levels.The expressions of Edg-4/LPA2 receptor mRNA were associated with tumor size,differentiation degree,and invasive ability and metastasis.While the expressions of Edg-2/LPA1,Edg-7/LPA3 receptor mRNA was associated with invasive ability and metastasis only.ConclusionsEdg-4/LPA2 receptor is highly expressed in pancreatic cancer,which suggesting the malignant biological behavior of pancreatic cancer.