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c—Met抑制剂SU11274对基底样乳腺癌MDA-MB-231细胞的影响 被引量：1

Effects of c-Met inhibitor SUl1274 on basal-like breast cancer cells MDA-MB-231
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摘要 目的研究c-Met抑制剂SUll274对c—Met阳性基底样乳腺癌细胞系MDA—MB-231凋亡和运动的影响。方法荧光染料Hoechst33342、MitroTrackerRed和Yo-pro-1染色，观察SU11274诱导细胞凋亡的形态学变化；流式细胞术检测不同处理组的细胞早期凋亡率；Westernblot检测凋亡相关蛋白的表达变化和c．Met及Akt磷酸化水平的改变；划痕试验及趋化试验观察SU11274对细胞迁移、趋化能力的影响。结果SUll274（10ixmol／L）处理MDA—MB-231细胞48h后，与对照组比较，荧光染色可见处理组细胞核绿染，胞核碎裂；各加药组MDA—MB-231的早期凋亡率分别为（7．3±0．9）％、（14．1±0．6）％、（35．5±4．4）％、（48．2±5．3）％，与对照组相比明显升高（P〈0．05）。同时，抗凋亡蛋白Bcl．XL表达减少，凋亡相关蛋白Caspase-3和PARP蛋白剪切增加，量效关系明显。SUll274可显著延长划痕愈合时间以及减少趋化穿膜细胞个数（P〈0．05），并有效抑制c-Met及Akt的磷酸化水平，呈剂量依赖性关系。结论SU11274可通过抑制c—Met／P13K／Akt的磷酸化水平而诱导c-Met阳性基底样乳腺癌细胞系MDA-MB-231凋亡，并抑制其运动。 Objective To investigate the effects of a new c-Met inhibitor SUl1274 on apoptosis and motility of c-Met-positive basal-like breast cancer cells MDA-MB-231. Methods The concentrations of SUl1274 were set to 0, 0. 1, 1, 10 and 20 μmol/L. Morphological change of apoptotic cells was analyzed by Hoechst33342, MitroTrackerRed and Yo-pro-1 staining. The apoptotic rate of MDA-MB-231 ceils were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins （Bcl-XL, Caspase-3 and PARP） and phosphorylation levels of c-Met and Akt were analyzed by Western blot. The capability of motility were measured by wound-healing assay and chemotaxis assay. Results After treatment by SUl1274（10 μmol/L） for 48 h, shrinking apoptotic cells of MDA-MB-231 was observed by flurescent microscope and nuclear fragmentation was seen. Annexin V/PI double-staining showed SU11274 induced apoptosis of MDA-MB-231 cells （P 〈 0. 05 ）, and the apoptotic rates were （7.3 ± 0.9） %, （ 14. 1 ± 0. 6） %, （35. 5 ± 4. 4） % and （48. 2 ± 5. 3） %, respectively. SU11274 downregulated the expression of Bcl- XL and promoted the dissection of Caspase-3 and PARP in a dose dependent relationship. SU11274 prolongs the wound-healing time, decreases the migration cell count （ P 〈 0. 05 ） and effectively inhibits the phosphorylation of c-Met and its downstream key proteins Akt in a dose-dependent manner. Conclusions C-Met inhibitor SU11274 induces apoptosis and inhibits the motility of c-Met-positive basal-like breast cancer cell line MDA-MB-231, probably through inhibiting phosphorylation of c-Met/PI3K/Akt.
作者 冯炜红 张斌 李媛媛 赵洪猛 张月 陈祖锦 刘博文 曹旭晨
机构地区 天津医科大学附属肿瘤医院乳腺一科天津市肿瘤防治重点实验室乳腺癌防治教育部重点实验室
出处 《中华普通外科杂志》 CSCD 北大核心 2012年第3期234-237,共4页 Chinese Journal of General Surgery
基金 国家自然科学基金资助项目（81001186） 天津市自然科学基金资助项目（10JCYBJC14100）
关键词 乳腺肿瘤 癌 基底细胞 原癌基因蛋白质C-MET 凋亡 Breast neoplasms Carcinoma, basal cell Proto-oncogene proteins c-met Apoptosis
分类号 R737.9 [医药卫生—肿瘤]
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参考文献12

  • 1Garcia S, Dales JP, Charafe-Jauffret E, et al. Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. Hum Pathol, 2007,38: 830-841.
  • 2Purl N, Ahmed S, Janamanchi V, et al. c-Met is a potentially new therapeutic target for treatment of human melanoma. Clin Cancer Res, 2007,13 : 2246-2253.
  • 3Ma PC, Jagadeeswaran R, Jagadeesh S, et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res, 2005, 65 : 1479-1488.
  • 4刘慧,范钦和,李霄,刘广珍.基底细胞样型乳腺癌的临床病理特点和预后意义[J].中华病理学杂志,2009,38(5):316-322. 被引量：10
  • 5Fulford LG, Reis-Filho JS, Ryder K, et al. Basal-like grade III invasive ductal carcinoma of the breast : patterns of metastasis and long-term survival. Breast Cancer Res, 2007, 9( 1 ) : R4.
  • 6Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox : primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res, 2007,13 : 2329-2334.
  • 7Ponzo MG, Lesurf R, Petkiewicz S, et al. Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. Proc Natl Acad Sci USA. 2009.106: 12903-12908.
  • 8Gastaldi S, Comoglio PM, Trusolino L. The Met oncogene and basal-like breast cancer: another culprit to watch out for? Breast Cancer Res, 2010,12 : 208.
  • 9Koon EC, Ma PC, Salgia R, et al. Effect of a c-Met-specific, ATP-competitive small-molecule inhibitor SU11274 on human ovarian carcinoma cell growth, motility, and invasion. Int J Gynecol Cancer, 2008, 18: 976-984.
  • 10Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell, 2007, 129: 1261-1274.

二级参考文献23

  • 1Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histovatholoaw. 1991. 19 (5) :403-410.
  • 2Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res, 2004, 10(16) :5367-5374.
  • 3Abd E1-Rehim DM, Pinder SE, Paish CE, et al. Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathal, 2004, 203(2) :661-671.
  • 4Rodriguez-Pinilla SM, Sarrio D, Honrado E, et al. Prognostic significance of basal-like phenotype and fascin expression in nodenegative invasive breast carcinomas. Clin Cancer Res, 2006,12 (5) : 1533-1539.
  • 5Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature, 2000, 406 (6797) :747-752.
  • 6Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A,2001, 98 (19) :10869- 10874.
  • 7Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A, 2003, 100(14) :8418-8423.
  • 8Foulkes WD, Brunet JS, Stefansson IM, et al. The prognostic implication of the basal-like (cyclin E high/p27 low/p53 +/ glomeruloid-microvascular-proliferation + ) phenotype of BRCA1- related breast cancer. Cancer Res, 2004, 64(3) :830-835.
  • 9Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA, 2006, 295(21 ):2492-2502.
  • 10Calza S, Hall P, Auer G, et al. Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients. Breast Cancer Res, 2006, 8(4) :R34.

共引文献9

同被引文献24

  • 1lhemelandu C U, Leffall L D Jr, Dewitty R L, et al. Molecular breast cancer subtypes in premenopansal and postmenopausal Afri- can-American women : age-specific prevalence and survival [ J ]. J Surg Res, 2007,143(1) :109 -18.
  • 2Stefansson 0 A, Jonasson J G, Johannsson 0 T, et al. Genomic profiling of breast tumours in relation to BRCA abnormalities and phenotypes[ J]. Breast Cancer Res, 2009,11 (4) :R47.
  • 3Sener S F, Winchester D J, Winchester D P, et al. The effects of hormone replacement therapy on postmenopausal breast cancer bi- ology and survival[ J ]. Am J Surg, 2009,197 ( 3 ) :403 - 7.
  • 4Buckley N E, Conlon S J, Jirstrom K, et al. The DehaNp63 pro- teins are key allies of BRCA1 in the prevention of basaMike breast cancer[J]. Cancer Res, 2011 ,71 (5) :1933 -44.
  • 5Mani6 E, Vincent-Salomon A, Lehmann-Che J, et al. High fre- quency of TP53 mutation in BRCA1 and sporadic basal-like carci- nomas but not in BRCA1 luminal breast tumors[J]. Cancer Res, 200969(2) :663 -71.
  • 6Graveel C R, DeGroot J D, Su Y, et al. Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer [ J]. Proc Natl Acad Sci USA, 2009,106 ( 31 ) : 12909 - 14.
  • 7Xu K, Usary J, Kousis P C, et al. Lunatic fringe deficiency coop- erates with the Met/Caveolin gene amplicon to induce basal-like breast cancer[ J]. Cancer Cell, 2012,2t (5) :626 -41.
  • 8Yamakuchi M, Lowenstein C J. MiR-34, SIRT1 and p53: the feedback loop[J]. Cell Cycle, 2009,8(5) :712 -5.
  • 9Svoboda M, Sana J, Redova M, et al. MiR-34b is associated withclinical outcome in triple - negative breast cancer patients[ J]. Di- agn Pathol, 2012,7:31.
  • 10Iorio M V, Ferracin M, Liu C G, et al. MicroRNA gene expres- sion deregulation in human breast cancer[ J. Cancer Res, 2005, 65(16) :7065 -70.

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中华普通外科杂志
2012年 第3期

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