雷公藤红素对胃癌细胞增殖及有氧糖酵解的影响
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摘要
目的探究雷公藤红素对胃癌细胞BGC-823增殖及有氧糖酵解的影响。方法 BGC-823细胞经雷公藤红素处理后,CCK8实验与克隆形成实验检测细胞增殖能力;流式细胞术检测细胞凋亡与周期;分光光度计法检测细胞葡萄糖消耗量、乳酸生成量及己糖激酶(HK)、乳酸脱氢酶(LDH)活性变化;Western blot检测BGC-823细胞内葡萄糖转运体1(GLUT1)、己糖激酶Ⅱ亚型(HKⅡ)、丙酮酸激酶M2亚型(PKM2)、LDH蛋白表达。结果雷公藤红素作用后,BGC-823细胞增殖受到抑制,细胞凋亡增加,细胞周期阻滞于G2/M期。BGC-823细胞葡萄糖利用量及乳酸生成量降低,GLUT1、HKⅡ及LDH蛋白表达下降,HK、LDH酶活性受抑制。结论雷公藤红素抑制BGC-823细胞增殖,其作用可能与抑制细胞有氧糖酵解有关。
Objective To explore the effects of celastrol on the proliferation and aerobic glycolysis of gastric cancer cell line BGC-823. Methods After treatment with celastrol, the proliferation of BGC-823 cells was detected by CCK8 assay and clone formation assay; cell apoptosis and cell cycle distribution were detected by flow cytometry. Glucose utilization, lactic acid production, hexokinase(HK) activity and lactate dehydrogenase(LDH) activity were detected by spectorphotometry; Western blot was conducted to detect the expressions of glucose transporter 1(GLUT1), hexokinase Ⅱ(HKⅡ), pyruvate kinase M2(PKM2), and LDH in BGC-823 cells. Results Exposed to celastrol, BGC-823 cells' proliferation was inhibited, cell apoptosis was induced, and cell cycle was blocked in G2 phase. Glucose utilization and lactate production were decreased. Moreover, celastrol downregulated the expressions of GLUT1, HKII, and LDH protein as well as the activities of HK and LDH enzyme. Conclusion Celastrol can inhibit the proliferation of BGC-823 cells and it may be related to the inhibition of aerobic glycolysis.
Objective To explore the effects of celastrol on the proliferation and aerobic glycolysis of gastric cancer cell line BGC-823. Methods After treatment with celastrol, the proliferation of BGC-823 cells was detected by CCK8 assay and clone formation assay; cell apoptosis and cell cycle distribution were detected by flow cytometry. Glucose utilization, lactic acid production, hexokinase(HK) activity and lactate dehydrogenase(LDH) activity were detected by spectorphotometry; Western blot was conducted to detect the expressions of glucose transporter 1(GLUT1), hexokinase Ⅱ(HKⅡ), pyruvate kinase M2(PKM2), and LDH in BGC-823 cells. Results Exposed to celastrol, BGC-823 cells' proliferation was inhibited, cell apoptosis was induced, and cell cycle was blocked in G2 phase. Glucose utilization and lactate production were decreased. Moreover, celastrol downregulated the expressions of GLUT1, HKII, and LDH protein as well as the activities of HK and LDH enzyme. Conclusion Celastrol can inhibit the proliferation of BGC-823 cells and it may be related to the inhibition of aerobic glycolysis.
引文
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[2] WARBURG O.On the origin of cancer cells[J].Science,1956,123(3191):309-314.
[3] WARBURG O.On respiratory impairment in cancer cells[J].Science,1956,124(3215):267-269.
[4] GALLUZZI L,KEPP O,HEIDEN MG,et al.Metabolic targets for cancer therapy [J].Nat Rev Drug Discov,2013,12(12):829-846.
[5] 王淑静,董立强,刘欢,等.雷公藤红素对SGC-7901细胞和ECV304细胞增殖及能量代谢的影响 [J].中草药,2016,47(21):3854-3860.
[6] KANNAIYAN R,SHANMUGAM MK,SETHI G.Molecular targets of celastrol derived from Thunder of God Vine:Potential role in the treatment of inflammatory disorders and cancer[J].Cancer Lett,2011,303(1):9-20.
[7] KANNAIYAN R,MANU KA,CHEN L,et al.Celastrol inhibits tumor cell proliferation and promotes apoptosis through the activation of c-Jun N-terminal kinase and suppression of PI3 K/Akt signaling pathways[J].Apoptosis,2011,16(10):1028-1041.
[8] 袁菱,童德银.雷公藤红素及其制剂的抗肿瘤研究进展[J].中国医院药学杂志,2016,36(14):1224-1229.
[9] 龚建军,胡永胜.雷公藤红素对神经胶质瘤U87细胞增殖、凋亡和迁移的影响[J].中草药,2017,48(24):5194-5199.
[10] SALMINEN A,LEHTONEN M,PAIMELA T,et al.Celastrol:Molecular targets of Thunder God Vine[J].Biochem Biophys Res Commun,2010,394(3):439-442.
[11] DOUGLAS H,ROBERTA W.Hallmarks of cancer:The next generation [J].Cell,2011,144(5):646-647.
[12] FOUAD YA,AANEI C.Revisiting the hallmarks of cancer[J].Am J Cancer Res,2017,7(5):1016-1036.
[13] MA J,HAN LZ,LIANG H,et al.Celastrol inhibits the HIF-1α pathway by inhibition of mTOR/p70S6K/eIF4E and ERK1/2 phosphorylation in human hepatoma cells[J].Oncol Rep,2014,32(1):235-242.
[14] HUANG L,ZHANG Z,ZHANG S,et al.Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway[J].Int J Mol Med,2011,27(3):407-415.
[15] HU Y,QI Y,LIU H,et al.Effects of celastrol on human cervical cancer cells as revealed by ion-trap gas chromatography-mass spectrometry based metabolic profiling[J].Biochim Biophys Acta,2013,1830(3):2779-2789.
[16] HAY N.Reprogramming glucose metabolism in cancer:Can it be exploited for cancer therapy?[J].Nat Rev Cancer,2016,16(10):635-649.
[17] ORONSKY BT,ORONSKY N,FANGER GR,et al.Follow the ATP:tumor energy production:A perspective[J].Anticancer Agents Med Chem,2014,14(9):1187-1198.