Effects of saturated fatty acid and unsaturated fatty acid on the glucose metabolism of human lung adenocarcinoma A549 cells
LI Huimin1 LI Ning2 WU Jun3 CHEN Xi2 HE Zhan4 ZHANG Haitao2
1.Department of Laboratory, Tongde Hospital of Zhejiang Province, Zhejiang Province, Hangzhou 310012, China;
2.Department of Biochemistry and Molecular Biology, Guangdong Medical University, Guangdong Province, Zhanjiang 524023, China;
3.Department of Respiratory, Affiliated Hospital of Guangdong Medical University, Guangdong Province, Zhanjiang 524001, China;
4.Department of Pathology, Affiliated Hospital of Guangdong Medical University, Guangdong Province, Zhanjiang 524001, China
Abstract：Objective To analyze the effects of saturated fatty acid and unsaturated fatty acid on the glucose metabolism of lung adenocarcinoma A549 cells. Methods The liquid chromatography mass spectrometry (LC-MS/MS) assay was conducted by setting up the blank control group (cells were not treated), absolute ethanol solvent control group (the same volume of absolute ethanol as the drug in the drug treatment group was added into the cell culture medium), 120 μmol/L saturated fatty acid stearic acid group, 120 μmol/L unsaturated fatty acid docosahexaenoic acid (DHA) group, after A549 cells were treated for 24 hours respectively, and the relative content of acetyl-CoA in each group was detected; the Western blot assay was conducted by setting up the blank control group (cells were not treated), absolute ethanol solvent control group (the same volume of absolute ethanol as the drug in the drug treatment group was added into the cell culture medium), 120 μmol/L stearic acid group (A549 cells treated with 120 μmol/L stearic acid for 12, 24, 36 h respectively), 120 μmol/L DHA group (A549 cells treated with 120 μmol/L DHA for12, 24, 36 h respectively), the expression of glucose metabolism related proteins pyruvate kinase M2(PKM2), hexokinase 2(HK2), lactate dehydrogenase(LDH), pyruvate kinase M1 and pyruvate kinase M2 (PKM1/2) in A549 cells were detected. Results In LC-MS/MS assay, compared with the absolute ethanol solvent control group, the relative content of acetyl-CoA was reduced after A549 cells treated with 120 μmol/L stearic acid and DHA respectively, and the differences were statistically significant (P＜0.05). In Western blot assay, compared with the absolute ethanol solvent control group, the expression of PKM2, HK2, LDH, and PKM1/2 were reduced after A549 cells treated with 120 μmol/L stearic acid and DHA respectively for 12, 24, 36 h, and the differences were statistically significant (P＜0.05). Conclusion Saturated fatty acid and unsaturated fatty acid can inhibit the glucose metabolism of A549 cells.
[1] Siegel RL，Miller KD，Jemal A. Cancer statistics，2020[J].CA Cancer J Clin，2020，70（1）：7-30.
[2] Giard DJ，Aaronson SA，Todaro GJ，et al. In vitro cultivation of human tumors： Establishment of cell lines derived from a series of solid tumors[J]. J Natl Cancer Inst，1973，51（5）：1417-1423.
[3] Lieber M，Smith B，Szakal A，et al. A continuous tumor-cell line from a human lung carcinoma with properties of type Ⅱ alveolar epithelial cells[J]. Int J Cancer，1976，17（1）：62- 70.
[4] Wang Y，Yang H，Liu H，et al. Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells： an in vitro study [J]. BMC Cancer，2009，9：174.
[5] Mohtar N，Parumasivam T，Gazzali AM，et al. Advanced Nanoparticle- Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment [J].Cancers （Basel），2021，13（14）：3539.
[6] Alina ES，Yuri VF，Vladimir BT，et al. Photochemical synthesis，intercalation with DNA and antitumor evaluation in vitro of benzo[d]thiazolo[3，2-a]quinolin-10-ium derivatives [J].Bioorg Chem，2021，115：105267.
[7] Warburg O. The metabolism of carcinoma cells [J]. Journal of Cancer Research，1925，9（1）： 148 -163.
[8] Vaupel P，Schmidberger H，Mayer A. The Warburg effect： essential part of metabolic reprogramming and central contributor to cancer progression[J]. Int J Radiat Biol，2019，95（7）： 912-919.
[9] 李慧敏，伍俊，吴尚，等.饱和脂肪酸和不饱和脂肪酸对肺癌细胞增殖与自噬的影响[J].解放军医学杂志，2017， 42（8）： 668-673.
[10] Ganapathy-Kanniappan S，Geschwind JF. Tumor glycolysis as a target for cancer therapy： progress and prospects [J]. Mol Cancer ，2013，12：152.
[11] Dai W，Wang F，Lu J，et al. By reducing hexokinase 2，resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice [J]. Oncotarget ，2015，6（15）：13703-13717.
[12] Vaupel P，Multhoff G.Revisiting the Warburg effect： historical dogma versus current understanding [J]. J Physiol，2021，599（6）：1745-1757.
[13] Pietrocola F，Galluzzi L，Bravo-San Pedro JM，et al. Acetyl coenzyme A： a central metabolite and second messenger [J]. Cell Metab，2015，21（6） ： 805-821．
[14] Schug ZT，Peck B，Jones DT，et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress [J]. Cancer Cell，2015，27（1）：57-71
[15] Gao X，Lin SH，Ren F，et al. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia [J]. Nat Commun，2016，7：11960．
[16] Lin R，Tao R，Gao X，et al. Acetylation stabilizes ATP-Citrate lyase to promote lipid biosynthesis and tumor growth[J].Molecular Cell，2013，51（4）：506-518．
[17] Lu M，Zhu WW，Wang X，et al. ACOT12-Dependent alteration of acetyl-CoA drives hepatocellular carcinoma metastasis by epigenetic induction of epithelial-mesenchymal transition [J].Cell Metab，2019，29（4）： 886-900.
[18] Krasnov GS，Dmitriev AA，Lakunina VA，et al. Targeting VDAC-bound hexokinase Ⅱ： a promising approach for concomitant anticancer therapy[J]. Expert Opin Ther Targets，2013，17（10）：1221-1233.
[19] Yeh CS，Wang JY，Chung FY，et al. Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers[J]. Oncol Rep，2008， 19（1）：81-91.
[20] Alquraishi M，Puckett DL，Alani DS，et al. Pyruvate kinase M2： A simple molecule with complex functions[J]. Free Radic Biol Med，2019，143：176-192.
[21] Valvona CJ，Fillmore HL，Nunn PB，et al. The Regulation and Function of Lactate Dehydrogenase A： Therapeutic Potential in Brain Tumor[J]. Brain Pathol，2016，26（1）： 3-17.
[22] Seth P，Grant A，Tang J，et al. On-target inhibition of tumor fermentative glycolysis as visualized by hyperpolarized pyruvate [J]. Neoplasia，2011，13（1）：60-71.
[23] Suzuki A，Puri S，Leland P，et al. Subcellular compartmentalization of PKM2 identifies anti-PKM2 therapy response in vitro and in vivo mouse model of human non-small-cell lung cancer [J]. PLoS One，2019，14（5）：e217131.
[24] Li W，Gao F，Ma X，et al. Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases Ⅱ-mediated glycolysis [J]. Oncotarget，2017，8（20）：32586-32599.
[25] Liu L，He Y，Ge G，et al. Lactate dehydrogenase and creatine kinase as poor prognostic factors in lung cancer： A retrospective observational study [J]. PLoS One，2017，12（8）： e182168.
[26] Deng T，Zhang J，Meng Y，et al. Higher pretreatment lactate dehydrogenase concentration predicts worse overall survival in patients with lung cancer [J]. Medicine （Baltimore），2018， 97（38）：e12524.
京公网安备 11010502046598号