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氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响

王洁 黄岩 张川 马兴元 常文军 陆一鸣

王洁, 黄岩, 张川, 马兴元, 常文军, 陆一鸣. 氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响[J]. 药学实践与服务, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
引用本文: 王洁, 黄岩, 张川, 马兴元, 常文军, 陆一鸣. 氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响[J]. 药学实践与服务, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
WANG Jie, HUANG Yan, ZHANG Chuan, MA Xingyuan, CHANG Wenjun, LU Yiming. Effect of 5-FU on the expression of SHP2 gene in colorectal cancer cells RKO[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
Citation: WANG Jie, HUANG Yan, ZHANG Chuan, MA Xingyuan, CHANG Wenjun, LU Yiming. Effect of 5-FU on the expression of SHP2 gene in colorectal cancer cells RKO[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008

氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响

doi: 10.3969/j.issn.1006-0111.2017.06.008
基金项目: 国家自然科学基金资助项目(30500093,81274162);国家科技部"重大新药创制"专项(2009ZX09103-690);上海市科委生物医药领域科技支撑项目(16431904400);上海市教委科研创新项目(14ZZ077)

Effect of 5-FU on the expression of SHP2 gene in colorectal cancer cells RKO

  • 摘要: 目的 探究氟尿嘧啶(5-FU)对结直肠癌RKO细胞SHP2基因表达的影响。 方法 培养对数生长期的人结直肠癌细胞RKO,5-FU处理48 h后,采用免疫荧光和Western免疫印迹观察SHP2的蛋白表达水平;将能够特异性抑制SHP2表达的siRNA(siSHP2)转染RKO细胞,5-FU处理48 h,CCK8测定细胞吸光度(A)值,流式检测细胞凋亡,观察RKO对5-FU的敏感性变化及5-FU诱导细胞凋亡的影响。 结果 结直肠癌细胞RKO在5-FU处理48 h后,其细胞核中SHP2的蛋白表达水平明显增高;siSHP2转染后,RKO细胞对5-FU的敏感性降低,且降低了5-FU诱导的细胞凋亡率。 结论 5-FU可能通过影响SHP2的表达,促进RKO细胞的凋亡,发挥抑癌作用。
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    [2] Neel B G, Gu H, Pao L. The ‘Shp’ ing news:SH2 domain-containing tyrosine phosphatases in cell signaling[J]. Trends Biochem Sci, 2003, 28(6):284-293.
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    [5] Tartaglia M, Mehle E L, Goldberg R, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome[J]. Nat Genet, 2001, 29(4):465-468.
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    [8] 唐春兰, 周向东, 杨和平等. SHP2在非小细胞肺癌中的表达及意义[J]. 中国肺癌杂志, 2010, 13(2):98-101.
    [9] Martinelli S, Carta C, Flex E, et al. Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors[J]. Cancer Genet Cytogenet, 2006, 166(2):124-129.
    [10] Bentires-Alj M, Paez JG, David FS, et al. Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia[J]. Cancer Res, 2004, 64(24):8816-8820.
    [11] Sartore-Bianchi A, Siena S. Plasticity of resistance and sensitivity to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer[J]. Handb Exp Pharmacol,2017,DOI: 10.1007/164_2017_19.
    [12] Monteleone G, Franchi L, Fina D, et al. Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells[J]. Cell Death Differ, 2006, 13(2):202-211.
    [13] Dai Y, Jiao H, Teng G, et al. Embelin reduces colitis-associated tumorigenesis through limiting IL-6/STAT3 signaling[J]. Mol Cancer Ther, 2014, 13(5):1206-1216.
    [14] Chu EC, Chai J, Tarnawski AS. NSAIDs activate PTEN and other phosphatases in human colon cancer cells:novel mechanism for chemopreventive action of NSAIDs[J]. Biochem Biophys Res Commun, 2004, 320(3):875-879.
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    [16] Li S, Hsu DD, Wang H, et al. Dual faces of SH2-containing protein-tyrosine phosphatase Shp2/PTPN11 in tumorigenesis[J]. Front Med, 2012, 6(3):275-279.
    [17] Jakob S, Schroeder P, Lukosz M, et al. Nuclear protein tyrosine phosphatase Shp-2 is one important negative regulator of nuclear export of telomerase reverse transcriptase[J]. J Biol Chem, 2008, 283(48):33155-33161.
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    [19] Yuan L, Yu WM, Yuan Z, et al. Role of SHP-2 tyrosine phosphatase in the DNA damage-induced cell death response[J]. J Biol Chem,2003,278(17):15208-15216.
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  • 收稿日期:  2017-06-19
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氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响

doi: 10.3969/j.issn.1006-0111.2017.06.008
    基金项目:  国家自然科学基金资助项目(30500093,81274162);国家科技部"重大新药创制"专项(2009ZX09103-690);上海市科委生物医药领域科技支撑项目(16431904400);上海市教委科研创新项目(14ZZ077)

摘要: 目的 探究氟尿嘧啶(5-FU)对结直肠癌RKO细胞SHP2基因表达的影响。 方法 培养对数生长期的人结直肠癌细胞RKO,5-FU处理48 h后,采用免疫荧光和Western免疫印迹观察SHP2的蛋白表达水平;将能够特异性抑制SHP2表达的siRNA(siSHP2)转染RKO细胞,5-FU处理48 h,CCK8测定细胞吸光度(A)值,流式检测细胞凋亡,观察RKO对5-FU的敏感性变化及5-FU诱导细胞凋亡的影响。 结果 结直肠癌细胞RKO在5-FU处理48 h后,其细胞核中SHP2的蛋白表达水平明显增高;siSHP2转染后,RKO细胞对5-FU的敏感性降低,且降低了5-FU诱导的细胞凋亡率。 结论 5-FU可能通过影响SHP2的表达,促进RKO细胞的凋亡,发挥抑癌作用。

English Abstract

王洁, 黄岩, 张川, 马兴元, 常文军, 陆一鸣. 氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响[J]. 药学实践与服务, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
引用本文: 王洁, 黄岩, 张川, 马兴元, 常文军, 陆一鸣. 氟尿嘧啶对结直肠癌RKO细胞SHP2基因表达的影响[J]. 药学实践与服务, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
WANG Jie, HUANG Yan, ZHANG Chuan, MA Xingyuan, CHANG Wenjun, LU Yiming. Effect of 5-FU on the expression of SHP2 gene in colorectal cancer cells RKO[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
Citation: WANG Jie, HUANG Yan, ZHANG Chuan, MA Xingyuan, CHANG Wenjun, LU Yiming. Effect of 5-FU on the expression of SHP2 gene in colorectal cancer cells RKO[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(6): 512-515. doi: 10.3969/j.issn.1006-0111.2017.06.008
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