Abstract：Objective: To investigate the possible mechanism of mitochondrial autophagy in the progression of lung cancer by downregulating the Gas6/MerTK signaling pathway. Methods: Calu-1 and A-427 cell lines were cultured and divided into (1) control group, Gas6 intervention (downregulation of Gas6) group, (2) control group, rapamycin (autophagy inducer, RAPA) group. Western blotting was used to detect the protein expression levels of Gas6, MerTK, LC3Ⅱ, and Beclin1. Transmission electron microscopy was employed to observe autophagic vesicles in cells. Colony formation assay was conducted to assess the cloning ability of Calu-1 and A-427 cells. CCK-8 assay was performed to measure cell viability. Scratch assay was used to evaluate the migration ability of Calu-1 and A-427 cells. Immunofluorescence was utilized to detect the expression levels of LC3 in Calu-1 and A-427 cells. Results: Compared with the control group, the Gas6 intervention group showed a significant decrease in Gas6 and MerTK protein levels in Calu-1 and A-427 cells (P<0.05), a significant increase in LC3Ⅱ and Beclin1 protein levels (P<0.05), and the formation of autophagic vesicles with abundant autophagic vacuole accumulation. The cloning ability, cell viability, and migration distance of Calu-1 and A-427 cells were significantly reduced (P<0.05). Compared with the control group, the RAPA group exhibited an increase in LC3 protein expression in Calu-1 and A-427 cells (P<0.05). The cloning ability, cell viability, and migration distance of Calu-1 and A-427 cells were significantly reduced (P<0.05). Conclusion: Downregulating the Gas6/MerTK signaling pathway can induce mitochondrial autophagy in Calu-1 and A-427 cells and inhibit their proliferation, activity, and migration abilities.
[1] Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer Clin,2021,71(3):209-249. [2] Kordiak J,Bielec F,Jablonski S,et al.Role of beta-carotene in lung cancer primary chemoprevention:a systematic review with meta-analysis and meta-regression[J].Nutrients,2022,14(7):1361. [3] Du W,Zhu J,Zeng Y,et al.KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway[J].Cell Death Differ,2021,28(4):1284-1300. [4] Miao CC,Hwang W,Hu LY,et al.LC3A-mediated autophagy regulates lung cancer cell plasticity[J].Autophagy,2022,18(4):921-934. [5] Nooreldeen R,Bach H.Current and future development in lung cancer diagnosis[J].Int Mol Sci,2021,22(16):8661. [6] Cheung CHY,Juan HF.Quantitative proteomics in lung cancer[J].Biomed Sci,2017,24(1):37. [7] 吴军来,柴克霞.TAM/Gas6通路及其与临床疾病的关系[J].临床荟萃,2021,36(7):664-668. [8] 谢崧璞,刘承云.GAS6/TAM信号通路在止血和血栓形成中的作用研究进展[J].医学综述,2021,27(15):2924-2928. [9] Wu G,Ma Z,Cheng Y,et al.Targeting gas6/TAM in cancer cells and tumor microenvironment[J].Mol Cancer,2018,17(1):20. [10] Myers KV,Amend SR,Pienta KJ.Targeting tyro3,axl and merTK (TAM receptors):implications for macrophages in the tumor microenvironment[J].Mol Cancer,2019,18(1):94. [11] Liu Y,Lan L,Li Y,et al.N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth[J].Redox Biol,2022,54:102366. [12] Liu G,Pei F,Yang F,et al.Role of autophagy and apoptosis in non-small-cell lung cancer[J].Int Mol Sci,2017,18(2):367. [13] 谢利.Gas6调控自噬在石英粉尘致炎性反应中的作用研究[D].华中科技大学,2021. [14] 高雅婷,王心恒,王小乐,等.芪玉三龙汤调节mTOR/Beclin1/LC3信号轴相关分子的表达诱导肺癌A549细胞自噬[J].中国实验方剂学杂志,2021,27(1):98-104.
2023, Vol. 29 
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