目的 應用細胞外信號調節(jié)激酶(ERK)1/2抑制劑U0126研究ERK1/2在肝癌細胞增殖、凋亡中的作用。
方法 以肝癌SMMC-7721細胞株為材料,分為空白對照組及不同濃度的U0126處理組。以MTT檢測細胞增殖情況,流式細胞儀分析細胞周期及細胞凋亡情況。
結果 不同濃度的U0126處理后均可明顯抑制肝癌SMMC-7721細胞的增殖(P<0.05,P<0.01),使處于G0/G1期的細胞明顯增多(P<0.05)且呈劑量依賴性,并誘發(fā)細胞凋亡發(fā)生(P<0.05)。
結論 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通路誘導肝癌細胞SMMC-7721凋亡的研究. 中國普外基礎與臨床雜志, 2007, 14(6): 675-678. doi: 復制
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- 1. Bos JL. All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral [J]. EMBO J, 1998; 17(23)∶6776.
- 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. 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. 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. 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. 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. 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]. 生理科學進展, 2003; 33(2)∶111.
- 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 黃辰, 劉利英, 宋土生, 等. siRNA介導的MAPK p42沉默誘導HeLa細胞凋亡 [J]. 南方醫(yī)科大學學報, 2006; 26(1)∶11.
- 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. 黃辰, 劉利英, 宋土生, 等. 使用技術抑制細胞P42MAPK表達 [J]. 中華病理學雜志, 2006; 35(5)∶292.