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Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma
Institution:1. Pharmacology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Integrative Medicine, Jammu 180001, Jammu & Kashmir, India;2. Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, Uttar Pradesh, India;3. Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, Jammu & Kashmir, India;4. Pharmacokinetics-Pharmacodynamics (PK-PD), Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, Jammu & Kashmir, India;1. Department of Meridian & Acupoint, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;2. WHO Collaborating Center for Traditional Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea;3. Department of Meridian and Acupoint, College of Korean Medicine, Sang Ji University, Wonju 26339, Republic of Korea;1. School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China;2. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China;1. Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China;2. Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China;1. Department of Rehabilitation, Changhai Hospital, Naval Medical University, Shanghai 200433, China;2. Department of Traditional Chinese Medicine, The 920th Hospital of Joint Logistics Support Force, Kunming 650000, Yunnan Province, China;3. Second Team, Graduate School, Naval Medical University, Shanghai 200433, China;4. College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, Jiangsu Province, China;5. Department of Military Traditional Chinese Medicine, Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China;1. Department of Nursing, Chengdu Integrated TCM & Western Medicine Hospital, Sichuan 610041, Sichuan Province, China;2. School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China;3. Department of Nursing, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China;4. Department of General Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China;5. Department of Gynecology and Obstetrics, Guangzhou Women and Children’s Medical Center, Guangzhou 510120, Guangdong Province, China
Abstract:ObjectiveAlthough there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.MethodsSmall interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2′-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.ResultsJAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.ConclusionJAML is a novel target for kaempferol against LUAD cells.Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268–276.
Keywords:Junctional adhesion molecule-like protein  Kaempferol  Lung adenocarcinoma  Proliferation  Invasion  Migration
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