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The Pharmacological Mechanism of Curcumin against Drug Resistance in Non-Small Cell Lung Cancer: Findings of Network Pharmacology and Bioinformatics Analysis

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机构： [1]State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Wai Long, Macau. [2]School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. [3]Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, China. [4]Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, China. [5]Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. [6]Department of Respiratory, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China. [7]Guangdong-HongKong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou 510006, China. [8]Zhuhai MUST Science and Technology Research Institute, Zhuhai 519000, Guangdong, China. [9]Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai 519000, Guangdong, China.

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The pharmacological mechanism of curcumin against drug resistance in non-small cell lung cancer (NSCLC) remains unclear. This study aims to summarize the genes and pathways associated with curcumin action as an adjuvant therapy in NSCLC using network pharmacology, drug-likeness, pharmacokinetics, functional enrichment, protein-protein interaction (PPI) analysis, and molecular docking. Prognostic genes were identified from the curcumin-NSCLC intersection gene set for the following drug sensitivity analysis. Immunotherapy, chemotherapy, and targeted therapy sensitivity analyses were performed using external cohorts (GSE126044 and IMvigor210) and the CellMiner database. 94 curcumin-lung adenocarcinoma (LUAD) hub targets and 41 curcumin-lung squamous cell carcinoma (LUSC) hub targets were identified as prognostic genes. The anticancer effect of curcumin was observed in KEGG pathways involved with lung cancer, cancer therapy, and other cancers. Among the prognostic curcumin-NSCLC intersection genes, 20 LUAD and 8 LUSC genes were correlated with immunotherapy sensitivity in the GSE126044 NSCLC cohort; 30 LUAD and 13 LUSC genes were associated with immunotherapy sensitivity in the IMvigor210 cohort; and 12 LUAD and 13 LUSC genes were related to chemosensitivity in the CellMiner database. Moreover, 3 LUAD and 5 LUSC genes were involved in the response to targeted therapy in the CellMiner database. Curcumin regulates drug sensitivity in NSCLC by interacting with cell cycle, NF-kappa B, MAPK, Th17 cell differentiation signaling pathways, etc. Curcumin in combination with immunotherapy, chemotherapy, or targeted drugs has the potential to be effective for drug-resistant NSCLC. The findings of our study reveal the relevant key signaling pathways and targets of curcumin as an adjuvant therapy in the treatment of NSCLC, thus providing pharmacological evidence for further experimental research.Copyright © 2022 Han Xie et al.

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出版当年[2021]版：

大类 | 4 区医学

小类 | 4 区全科医学与补充医学

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第一作者：

第一作者机构： [1]State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Wai Long, Macau. [2]School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. [3]Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, China. [4]Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, China. [5]Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.

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通讯作者：

通讯机构： [1]State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Wai Long, Macau. [7]Guangdong-HongKong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou 510006, China. [8]Zhuhai MUST Science and Technology Research Institute, Zhuhai 519000, Guangdong, China. [9]Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai 519000, Guangdong, China.

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