Abstract:Objective: To investigate the effects of carthamin combined with miR-214 on the proliferation and apoptosis of lung cancer cells.Methods: Quantitative real-time PCR was conducted to determine miR-214 expression in human normal lung epithelial cells BEAS-2B and lung cancer cells A549 and H1299. miR-214 mimic (miR-214) and negative control (miR-NC) were transfected into A549 and H1299 cells. A549 and H1299 cells were divided into control, carthamin, miR-214 and carthamin +miR-214 groups. Cells in carthamin group were treated with 80μmoL/L carthamin, cells in miR-214 group were transfected with miR-214, and cells in carthamin+miR-214 group were co-treated with carthamin and miR-214. The cells without any treatment were used as control group. CCK-8, EdU and flow cytometry assays were performed to evaluate cell viability, proliferation, cell cycle and apoptosis, respectively. The protein expressions were analyzed with Western blot. A xenograft tumor model was used to evaluate the synergy of carthamin and miR-214 on lung cancer growth in vivo.Results: Compared with BEAS-2B cells, miR-214 expression was significantly reduced in A549 and H1299 cells. miR-214-transfected A549 and H1299 cells expressed higher level of miR-214, compared to miR-NC. Compared with control group, cell viability, EdU-positive cells and S-phase cells were markedly reduced, while G0/G1-phase cells and apoptotic cells were substantially increased in carthamin and miR-214 groups; the cell viability, EdU-positive cells and S-phase cells were less, while the G0/G1-phase cells and apoptotic cells were more in carthamin+miR-214 group than those in carthamin and miR-214 groups. Compared with control group, the phosphorylation of Akt and PI3K and protein expressions of Bcl-2, Cyclin D1 and CDK4 were considerably downregulated, while the expressions of Bax and cl-Caspase-3 were significantly up-regulated in carthamin and miR-214 groups. Akt and PI3K phosphorylations and protein levels of Bcl-2, Cyclin D1 and CDK4 in carthamin +miR-214 group were much lower, while Bax and cl-Caspase-3 expressions were higher than those in carthamin and miR-214 groups. In vivo experiments showed that compared with control group, the tumor volume and weight of mice were significantly reduced in carthamin and miR-214 groups, which were further smaller in carthamin+miR-214 group than those in carthamin and miR-214 groups.Conclusion: Carthamin combined with miR-214 could inhibit the proliferation but promote apoptosis of lung cancer cells in vitro and in vivo, probably through the inactivation of PI3K/Akt signaling pathway.
严涵, 郭绍兰, 戴学敏, 文馨悦, 杨英姿. 红花苷联合miR-214对肺癌细胞增殖及凋亡的作用[J]. 河北医学, 2024, 30(12): 1937-1944.
YAN Han, et al. Synergic Effects of Carthamin and miR-214 on Proliferation and Apoptosis of Lung Cancer Cells. HeBei Med, 2024, 30(12): 1937-1944.
[1] Bray F,Laversanne M,Sung H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer Clin,2024,74(3):229-263. [2] Ji HF,Yang ZQ,Han JJ,et al.Safflower yellow inhibits progression of hepatocellular carcinoma by modulating immunological tolerance via FAK pathway[J].Chin Integr Med,2024,30(4):339-347. [3] Tao W,Cao C,Ren G,et al.Circular RNA circCPA4 promotes tumorigenesis by regulating miR-214-3p/TGIF2 in lung cancer[J].Thorac Cancer,2021,12(24):3356-3369. [4] Zhao H,Wang Z,Wu G,et al.Role of microRNA-214 in dishevelled1-modulated β-catenin signalling in non-small cell lung cancer progression[J].Cancer,2023,14(2):239-249. [5] Fanini F,Bandini E,Plousiou M,et al.MicroRNA-16 Restores Sensitivity to Tyrosine Kinase Inhibitors and Outperforms MEK Inhibitors in KRAS-Mutated Non-Small Cell Lung Cancer[J].Int Mol Sci,2021,22(24):13357. [6] 赵军.红花苷对过氧化氢诱导的成骨细胞损伤的保护作用[J].沈阳药科大学学报,2021,38(11):1224-1231. [7] Kacaroglu D,Kalaycioglu GD,Ozden AK.Carthamus Tinctorius L.(Safflower) extracts inhibit expression of metastatic genes of MDA-MB-231 breast cancer cells[J].Cell Mol Biol (Noisy-le-grand),2023,69(12):19-25. [8] Lin K,Qin Z,Qu C,et al.Hydroxyl safflower yellow B combined with doxorubicin inhibits the proliferation of human breast cancer MCF-7 cells[J].Oncol Lett,2021,21(5):426. [9] Karimkhanloo H,Mohammadi-Yeganeh S,Hadavi R,et al.Potential role of miR-214 in β-catenin gene expression within hepatocellular carcinoma[J].Mol Biol Rep,2020,47(10):7429-7437. [10] Liu G,Shi H,Zheng H,et al.Circular RNA NFIX functions as an oncogene in non-small cell lung cancer by modulating the miR-214-3p/TRIAP1 axis[J].Clin Respir,2024,18(8):13801. [11] Arasi MB,De Luca G,Chronopoulou L,et al.MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance[J].Mol Ther,2024,32(1):152-167.