基于网络药理学和实验验证雷公藤红素治疗肾癌的作用及机制

doi:10.20047/j.issn1673-7210.2023.14.01

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Abstract Objective To investigate the effect and mechanism of Celastrol (CeT) in the treatment of renal carcinoma by network pharmacology, molecular docking techniques, and experimental verification methods. Methods The key targets and pathways of CeT in the treatment of renal carcinoma were analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, PubChem, NCBI Gene, STRING databases, GO function, and KEGG pathway enrichment, and then Autodock Vina software was used for molecular docking verification. Human renal clear cell adenocarcinoma cell line 786-O cells were selected and divided into control group (normal culture), and 0.2, 0.4, 0.8 ¦Ìmol/L CeT group (given the corresponding concentration of CeT). After 24 h culture, apoptotic proteins and related pathway proteins in each group were detected by Western blot. Results A total of 53 CeT targets and 8 881 disease targets were screened, and 45 common targets were obtained by mutual mapping. Core targets such as Bax and Bcl-2 were obtained by analyzing common targets of protein-protein interaction network. GO enrichment analysis obtained 469 items, KEGG pathway enrichment analysis identified 67 related pathways, including apoptosis, phosp- ha tidylinositol 3 kinase (PI3K) /Akt kinase (Akt) pathway, cysteine aspartic acid specific protease-9 (caspase-9), nuclear factor ¦ÊB (NF-¦ÊB), P53, and other signaling pathways. Molecular docking results showed that CeT had good binding activity with core targets. Cell experiment results showed that the expressions of caspase-9 and P53 in 0.4 and 0.8 ¦Ìmol/L CeT groups were higher than those in the control group, while the expressions of Bcl-2 and NF-¦ÊB were lower than those in the control group, the expression of Bax in 0.4 ¦Ìmol/L CeT group was higher than that in control group, expression of PI3K in 0.8 ¦Ìmol/L CeT group was lower than that in control group, the expressions of P-Akt /Akt in 0.2, 0.4, and 0.8 ¦Ìmol/L CeT groups were lower than those in control group, and the differences were statistically significant (P£¼0.05). The expression of NF-¦ÊB in 0.8 ¦Ìmol/L CeT group was lower than that in 0.2 ¦Ìmol/L CeT group, and the differences were statistically significant (P£¼0.05). Conclusion CeT may affect the expression of target proteins such as Bax and Bcl-2 through PI3K/Akt pathway, NF-¦ÊB, and P53 signaling pathways, and play a role of multi-target and multi-pathway treatment for renal carcinoma.

Key words： Renal carcinoma Celastrol Network pharmacology Molecular docking Effect and mechanism

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	YAN Tao1 GU Jia1??ZHU Neng2??SHI Yaning1 ZHANG Chanjuan1??LI Hongfang1??QIN Li1

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YAN Tao1 GU Jia1??ZHU Neng2??SHI Yaning1 ZHANG Chanjuan1??LI Hongfang1??QIN Li1. Effect and mechanism of Celastrol in the treatment of renal carcinoma based on network pharmacology and experimental verification[J]. 中国医药导报, 2023, 20(14): 4-10.

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