• 1.西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院普外科（西安710061）;;
  • 2.西安交通大學(xué)環(huán)境與腫瘤相關(guān)基因教育部重點(diǎn)實(shí)驗(yàn)室生物醫(yī)學(xué)基礎(chǔ)研究中心（西安710061）;

目的 　應(yīng)用細(xì)胞外信號調(diào)節(jié)激酶(ERK)1/2抑制劑U0126研究ERK1/2在肝癌細(xì)胞增殖、凋亡中的作用。
方法 　以肝癌SMMC-7721細(xì)胞株為材料，分為空白對照組及不同濃度的U0126處理組。以MTT檢測細(xì)胞增殖情況，流式細(xì)胞儀分析細(xì)胞周期及細(xì)胞凋亡情況。
結(jié)果 　不同濃度的U0126處理后均可明顯抑制肝癌SMMC-7721細(xì)胞的增殖（P＜0.05，P＜0.01）,使處于G0/G1期的細(xì)胞明顯增多（P＜0.05）且呈劑量依賴性，并誘發(fā)細(xì)胞凋亡發(fā)生（P＜0.05）。
結(jié)論　 阻斷ERK1/2通路有可能成為肝癌治療的重要手段。

引用本文： 盛薇,王康,平高峰,李徐奇,魏光兵,黃辰. 通過抑制ERK1/2通路誘導(dǎo)肝癌細(xì)胞SMMC-7721凋亡的研究. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(6): 675-678. doi: 復(fù)制

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  2. 2. 　Steinmetz R, Wagoner HA, Zeng P, et al. Mechanisms regulating the constitutive activation of the ERK signaling pathway in ovarian cancer and the effect of RNAi for ERK1/2 on cancer cell proliferation [J]. Mol Endocrino, 2004; 15(3)∶1004.
  3. 3. 　Wu TT, Wang JS, Jiaan BP, et al. Role of p21(WAF1) and p27(KIP1) in predicting biochemical recurrence for organ-confined prostate adenocarcinoma [J]. J Chin Med Assoc， 2007; 70(1)∶11.
  4. 4. 　Handra-Luca A, Bilal H, Bertrand JC, et al. Extra-cellular signal-regulated ERK-1/ERK-2 pathway activation in human salivary gland mucoepidermoid carcinoma: association to aggressive tumor behavior and tumor cell proliferation [J]. Am J Pathol， 2003; 163(3)∶957.
  5. 5. 　Hoshino R, Chatani Y, Yamori T, et al. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors [J]. Oncogene， 1999; 18(3)∶813.
  6. 6. 　Mishima K, Inoue K, Hayashi Y. Overexpression of extracellular-signal regulated kinases on oral squamous cell carcinoma [J]. Oral Oncol， 2002; 38(5)∶468.
  7. 7. 　鄭銘， 張幼怡， 韓啟德. β腎上腺素受體的絲裂原活化蛋白激酶信號途徑 [J]. 生理科學(xué)進(jìn)展, 2003; 33(2)∶111.
  8. 8. 　Kolch W. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions [J]. Biochem J， 2000; 351（Pt 2）∶289.
  9. 9. 　Gysin S, Lee SH, Dean NM, et al. Pharmacologic inhibition of RAF→MEK→ERK signaling elicits pancreatic cancer cell cycle arrest through induced expression of p27Kip1 [J]. Cancer Res， 2005; 65(11)∶4870.
  10. 10. 　Ito Y, Sasaki Y, Horimoto M, et al. Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma [J]. Hepatology， 1998; 27(4)∶951.
  11. 11. 　Adeyinka A, Nui Y, Cherlet T, et al. Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression [J]. Clin Cancer Res， 2002; 8(6)∶1747.
  12. 12. 　Albanell J, Codony-Servat J, Rojo F, et al. Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments [J]. Cancer Res， 2001; 61(17)∶6500.
  13. 13. 　Uzgare AR, Kaplan PJ, Greenberg NM. Differential expression and/or activation of P38MAPK, erk1/2, and jnk during the initiation and progression of prostate cancer [J]. Prostate， 2003; 55(2)∶128.
  14. 14. 　Rincon-Arano H, Rosales R, Mora N, et al. R-Ras promotes tumor growth of cervical epithelial cells [J]. Cancer， 2003; 97(3)∶575.
  15. 15. 　Gioeli D, Mandell JW, Petroni GR, et al. Activation of mitogen-activated protein kinase associated with prostate cancer progression [J]. Cancer Res， 1999; 59(2)∶279.
  16. 16. 　Anders M, Christian C, McMahon M, et al. Inhibition of the Raf/MEK/ERK pathway up-regulates expression of the coxsackievirus and adenovirus receptor in cancer cells [J]. Cancer Res， 2003; 63(9)∶2088.
  17. 17. 　Wen J, Zhang Y, Chen X, et al. Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells [J]. Biochem Pharmacol， 2004; 68(2)∶323.
  18. 18. 　黃辰， 劉利英， 宋土生， 等. siRNA介導(dǎo)的MAPK p42沉默誘導(dǎo)HeLa細(xì)胞凋亡 [J]. 南方醫(yī)科大學(xué)學(xué)報(bào)， 2006; 26(1)∶11.
  19. 19. 　Tamemoto H, Kadowaki T, Tobe K, et al. Biphasic activation of two mitogen-activated protein kinases during the cell cycle in mammalian cells [J]. J Biol Chem， 1992; 267(28)∶20293.
  20. 20. 　黃辰， 劉利英， 宋土生， 等. 使用技術(shù)抑制細(xì)胞P42MAPK表達(dá) [J]. 中華病理學(xué)雜志, 2006； 35(5)∶292.