Cancer Management and Research (Jan 2021)
Liver Kinase B1 (LKB1) Regulates Proliferation and Apoptosis of Non-Small Cell Lung Cancer A549 Cells via Targeting ERK Signaling Pathway
Abstract
Yirong Wang,1,* Lei Yang,2,* Yan Yang,3 Yulin Li4 1Department of Radiotherapy, Yantaishan Hospital, Yantai 264000, People’s Republic of China; 2Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan 250013, People’s Republic of China; 3Department of Respiratory and Critical Care, Shandong Provincial Chest Hospital, Jinan 250013, People’s Republic of China; 4Department of Oncology, Yantai Hospital of Traditional Chinese Medicine, Yantai 264000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yulin LiDepartment of Oncology, Yantai Hospital of Traditional Chinese Medicine, No. 39 Xingfu Road, Zhifu District, Yantai 264000, People’s Republic of ChinaTel +86 15063820695Fax +86 535-6597122Email [email protected]: To study the effect and potential mechanism of LKB1 on non-small cell lung cancer (NSCLC) A549 cells.Material and Methods: A549 cells were divided into control group, LKB1 negative control (NC) group, LKB1 group, ERK inhibitor group and LKB1 + ERK activator group. Cell proliferation and apoptosis were detected by cell counting kit (CCK-8) assay and flow cytometry, respectively. Transwell assay was used to analyze the invasion ability of A549 cells. The expression of apoptosis and ERK signaling pathway-related proteins were studied by Western blot. Furthermore, a nude mouse xenograft model was constructed and treated with LKB1, ERK inhibitor and activator, respectively. The tumor volume and tumor weight were measured. Immunohistochemistry was used to test the expression of Ki-67 protein in tumor tissues, and TUNEL staining was used to test the apoptosis. Moreover, Western blot was used to detect ERK signaling pathway-related proteins in tumor tissues.Results: Compared with control and NC groups, cell proliferation and invasion were inhibited in ERK inhibitor and LKB1 groups, while apoptosis and apoptosis-related proteins were increased (p < 0.05). Further study showed that ERK activator can reverse the effect of LKB1 in A549 cells. In nude mice, ERK inhibitor and LKB1 can reduce cell tumorigenicity and inhibit proliferation. Apoptosis was increased by ERK inhibitor and LKB1 treatment. Western blot showed that LKB1 and ERK inhibitor could reduce the protein expression of p-ERK1/2. However, the indicators above were the opposite in the ERK activator group.Conclusion: LKB1 overexpression can inhibit proliferation and promote apoptosis of NSCLC A549 cells, and its mechanism may be related to inhibition of the ERK signaling pathway.Keywords: LKB1, proliferation, apoptosis, ERK signaling pathway, lung cancer
