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PKM2 siRNA对人甲状腺乳头状癌细胞生长和增殖的影响 被引量:6

Effect of PKM2 siRNA on growth and proliferation of papillary thyroid cancer cell
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摘要 目的:研究PKM2在甲状腺乳头状癌(PTC)中的表达特性及其在PTC中的作用。方法:用抗PKM2的小干扰RNA转染PTC细胞。Western blot和RT-PCR技术分析细胞中PKM2的表达。MTT法和细胞平板克隆形成实验评估细胞的生长和增殖。采用乳酸、ATP和葡萄糖试剂盒分别测定细胞代谢产生的乳酸、ATP及消耗的葡萄糖。结果:PKM2在PTC中异常高表达。在PTC细胞系中应用特异性抗PKM2 siRNA可延缓细胞生长并降低其克隆形成能力。PKM2 siRNA可降低PTC细胞乳酸、ATP的产生,减少葡萄糖的消耗。结论:PKM2高表达可通过激活糖酵解的方式使PTC细胞具有选择性生长优势。PKM2异常高表达可能作为新的生物标记物,并成为PTC的潜在治疗靶点。 Objective:To investigate the expression pattern of PKM2 in papillary thyroid cancer(PTC) and the possible role of PKM2 in PTC.Methods:PTC cells were transfected with small interfering RNA against PKM2.PKM2 expression in cells was analyzed by Western blot and RT-PCR.Cell growth and proliferation was evaluated by MTT assays and colony formation assays.Lactate and ATP production and glucose consumption by cells were determined using commercial assay kits.Results:PKM2 was aberrantly overexpressed in PTC.Specific siRNA against PKM2 in PTC cell lines retarded cell growth and decreased their colony-forming capability.PKM2 knockdown also reduced lactate and ATP production,and glucose consumption by PTC cells.Conclusion:Overexpression of PKM2 provides a selective growth advantage for PTC cells through activation of glycolysis.Aberrant PKM2 overexpression may serve as a novel biomarker and a potential treatment target for PTC.
出处 《现代肿瘤医学》 CAS 2014年第2期278-282,共5页 Journal of Modern Oncology
基金 国家自然科学基金(编号:81200246)
关键词 甲状腺乳头状癌 PKM2 RNA干扰 糖酵解 papillary thyroid cancer PKM2 siRNA glycolysis
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  • 1Presek P, Reinacher M, Eigenbrodt E. Pyruvate kinase type M2 is phosphory- lated at tyrosine residues in cells trans- formed by Rous sarcoma virus. FEBS Lett 1988; 242:194-198.
  • 2Spoden GA, Morandell D, Ehehalt D, et al. The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2. J Cell Bio- chem 2009; 107:293-302.
  • 3Hoshino A, Hirst JA, Fujii H. Regula- tion of cell proliferation by interleukin- 3-induced nuclear translocation of pyruvate kinase. J Biol Chem 2007; 282:17706-17711.
  • 4lgnacak J, Stachurska MB. The dual ac- tivity of pyruvate kinase type M2 from chromatin extracts of neoplastic cells. Comp Biochem Physiol B Biochem Mol Bio/ 2003; 134:425-433.
  • 5Stetfik A, Veress R, Ovfidi J, Csermely P, Kdri G, UIIrich A. Nuclear translo- cation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res 2007; 67:1602- 1608.
  • 6Christofk HR, Vander Heiden MG, Har- ris MH, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumor growth. Nature 2008; 452:230-233.
  • 7Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate ki- nase M2 is a phosphotyrosine-binding protein. Nature 2008; 452:181 - 186.
  • 8Hitosugi T, Kang S, Vander Heiden MG. et al. Tyrosine phosphorylationinhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2009; 2:ra73.
  • 9Luo W, Hu H, Chang R, et al. Pyruvate kinase M2 is a PHD3-stimulated co- activator for hypoxiainducible factor 1. Cell 2011; 145:732-744.
  • 10Yang W, Xia Y, Ji H, et al. Nuclear PKM2 regulates beta-catenin transac- tivation upon EGFR activation. Nature 2011; 480:118-122.

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  • 1Evans JM,Donnelly LA,Emslie-Smith AM,et al.Metformin and reduced risk of cancer in diabetic patients[J].BMJ,2005,330(7503):1304-1305.
  • 2Klubo-Gwiezdzinska J,Costello J,Patel A,et al.Treatment with metformin is associated with higher remission rate in diabetic patients with thyroid cancer[J].J Clin Endocrinol Metab,2013,98(8):3269-3279.
  • 3Klubo-Gwiezdzinska J,Jensen K,Costello J,et al.Metformin inhibits growth and decreases resistance to anoikis in medullary thyroid cancer cells[J].Endocr Relat Cancer,2012,19(3):447-456.
  • 4Chen G,Xu S,Renko K,et al.Metformin inhibits growth of thyroid carcinoma cells,suppresses self-renewal of derived cancer stem cells,and potentiates the effect of chemotherapeutic agents[J].J Clin Endocrinol Metab,2012,97(4):E510-E520.
  • 5Vander Heiden MG,Cantley LC,Thompson CB.Understanding the warburg effect:the metabolic requirements of cell proliferation[J].Science,2009,324(5930):1029-1033.
  • 6Feng C,Gao Y,Wang C,et al.Aberrant overexpression of pyruvate kinase M2 is associated with aggressive tumor features and the BRAF mutation in papillary thyroid cancer[J].J Clin Endocrinol Metab,2013,98(9):E1524-E1533.
  • 7Smith U,Gale EA.Cancer and diabetes:are we ready for prime time[J]?Diabetologia,2010,53(8):1541-1544.
  • 8Belda-Iniesta C,Pernía O,Simó R.Metformin:a new option in cancer treatment[J].Clin Transl Oncol,2011,13(6):363-367.
  • 9Hawley SA,Boudeau J,Reid JL,et al.Complexes between the LKB1 tumor suppressor,STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade[J].J Biol,2003,2(4):28.
  • 10Ben Sahra I,Tanti JF,Bost F.The combination of metformin and 2-deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells[J].Autophagy,2010,6(5):670-671.

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