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PI3K/Akt与染料木黄酮增敏阿霉素体外化疗人乳腺癌MDA-MB-453细胞的关系研究 被引量:1

Relationship between PI3K/Akt pathway and genistein sensitizing human breast cancer MDA-MB-453 cell line to doxorubicin in vitro
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摘要 目的观察染料木黄酮(GEN)对HER2/neu高表达人乳腺癌MDA-MB-453细胞PI3K/Akt信号途径的抑制作用,探讨其在GEN增敏阿霉素(DOX)体外化疗乳腺癌MDA-MB-453细胞中的作用。方法GEN、PI3K特异性抑制剂渥曼青霉素(WT)和DOX单独或联合处理体外培养的MDA-MB-453细胞,免疫细胞化学法检测HER-2/neu蛋白表达,免疫印迹法检测总Akt和磷酸化Akt蛋白(p-Akt)表达。结果GEN对MDA-MB-453细胞HER2/neu和总Akt蛋白没有明显影响,但可明显降低p-Akt蛋白水平;同时WT也能明显降低p-Akt蛋白,并显著增强DOX抑制MDA-MB-453细胞生长的作用。结论GEN增敏DOX体外化疗乳腺癌MDA-MB-453细胞株可能与其抑制PI3K/Akt信号途径有关。 Objective To investigate the inhibitory effect of genistein on PI3K/Akt signal pathway in HER2/neu-overexpressing breast cancer MDA-MB-453 cells and the role of PI3K/Akt signal pathway in genistein sensitizing MDA-MB-453 cells to chemotherapeutic agent doxorubicin in vitro. Methods MDA-MB-453 breast cancer cells were treated with genistein or wortmannin or doxorubicin or genistein + doxorubicin or wortmannin + doxorubicin in vitro. The expressions of HER2/neu protein and Akt and p-Akt protein in MDA-MB-453 cells were observed by immunocytochemistry and Western blotting, respectively. Results Genistein did not change the expression of HER2/neu or total Akt protein in MDA-MB-453 cells, but significantly decreased phosphorylated Akt (p-Akt) level. Wortmannin also obviously decreased the p-Akt protein in MDA-MB-453 cells and sensitized the cells to the chemotherapeutic agent doxorubicin. Cenistein Genistein sensitizing MDA-MB-453 cells to doxombiein in vitro may be correlated with the inhibition of PI3K/Akt signal pathway.
出处 《免疫学杂志》 CAS CSCD 北大核心 2007年第2期225-228,共4页 Immunological Journal
关键词 染料木黄酮 阿霉素 人乳腺癌细胞株MDA-MB-453 HER2/NEU Akt Genistein Doxorubicin Human breast cancer cell line MDA- MB-453 HER-2/neu Akt
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参考文献10

  • 1Menard S, Pupa SM, Campiglio M, et al. Biologic and therapeutic role of HER2 in cancer [ J ]. Oncogene, 2003,22 (42) : 6 570 - 6 578.
  • 2Sarkar FH, Adsule S, Padhye S, et al. The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy [J]. Mini Rev Med Chem, 2006, 6 (4):401-407.
  • 3张红,朱俊东,糜漫天,郎海滨,彭俊华.三羟异黄酮与化疗药物联合作用对人乳腺癌细胞株MDA-MB-453增殖的影响[J].第三军医大学学报,2006,28(7):710-713. 被引量:11
  • 4Knuefermann C,Lu Y, Liu B, et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells[J]. Oncogene, 2003, 22 (21): 3 205 -3 212.
  • 5Yu D , Hung MC . Overexpression of ErbB 2 in cancer and ErbB2-targeting strategies [ J ]. Oncogene, 2000, 19 (53) :6 115- 6 121.
  • 6Kaufmann SH, Earnshaw WC. Induction of apptosis by cancer chemotherapy[J]. Exp Cell Res, 2000, 256(1):42-49.
  • 7Stephens L, Anderson K, Stokoe D, et al. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphatedependent activation of protein kinase B[J]. Science, 1998,279 (5 351) : 710 - 714.
  • 8Wang JM, Chao JR, Chen W, et al. The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex conmining CREB [J]. Mol Cell Biol, 1999, 19 (9):6 195-6206.
  • 9Harari D , Yarden Y . Molecular mechanisms underlying ErbB2/HER2 action in breast cancer[J]. Oncogene, 2000,19 (53): 6 102-6 114.
  • 10余小平,糜漫天,朱俊东.染料木黄酮对MDA-MB-453乳腺癌细胞uPA表达及PTK活性的影响研究[J].营养学报,2004,26(3):211-215. 被引量:5

二级参考文献23

  • 1王斌,糜漫天,彭俊华,朱俊东.辛基酚和三羟异黄酮对大鼠乳腺癌发生及细胞增殖影响的研究[J].第三军医大学学报,2005,27(2):119-122. 被引量:11
  • 2周永,糜漫天,杨镇洲.三羟异黄酮对辐射损伤小鼠骨髓基质细胞的保护作用[J].第三军医大学学报,2005,27(6):471-473. 被引量:5
  • 3[1]Polkowski K, Mazurek AP. Biological properties of genistein. A review of in vitro and in vivo data[J]. Acta Pol Pharm, 2000, 57:135-155.
  • 4[2]Robert S. Kerbel. Tumor angiogenesis: past,present,and the near future[J].Carcinogenesis, 2000,21:505-515.
  • 5[3]Etoh T, Inoue H, Tanaka S, et al. Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases[J]. Cancer Res, 2001,61: 2145-2153.
  • 6[4]Rabbani SA. Metalloproteinase and urokinase in angiogenesis and tumor progression[J]. In Vivo, 1998,12: 135-142.
  • 7[5]Watabe T, Yoshida K, Shindoh M,et al.The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor[J]. Int J. Cancer, 1998 ,77: 128-137.
  • 8[6]Allgayer H, Babic R, Gruetzner KU, et al. c-erbB-2 is of independent prognostic rele-vance in gastric cancer and is associated with the expression of tumor-associated protease systems[J]. J Clin Oncol, 2000,18:2201-2209.
  • 9[7]Zhao H, Morimoto T, Sasa M,et al. Immunohis-tochemical expression of uPA, PAI-1, cathepsin D and apoptotic cells in ductal carcinoma in situ of the breast[J]. Breast Cancer, 2002,9: 118-126.
  • 10[8]Jumper C, Cobos E, Lox C. The circulating urokinase plasminogen activator (uPA) and its soluble receptor (suPAR) are not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced non-small cell lung cancer (NSCLC) [J]. Anticancer Res, 2002, 22:2073-2076.

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同被引文献12

  • 1刘颖,卢琳,那晓琳,迟晓星,崔洪斌.Rb基因在染料木黄酮抑制人乳腺癌细胞生长中的作用[J].营养学报,2005,27(3):218-221. 被引量:1
  • 2余小平,糜漫天,朱俊东.染料木黄酮对MDA-MB-453乳腺癌细胞VEGF表达的影响[J].营养学报,2005,27(4):322-325. 被引量:9
  • 3余小平,糜漫天,朱俊东.木黄酮对MCF-7/HER-2细胞uPA表达影响[J].中国公共卫生,2006,22(8):937-939. 被引量:4
  • 4宋鸣子,戈应滨,范玲玲,李迎春,顾洛.染料木黄酮对人乳腺癌细胞肌动蛋白细胞骨架和黏附能力的影响[J].南京医科大学学报(自然科学版),2007,27(5):424-427. 被引量:6
  • 5Wang TY,Sathyamoorthy N,Phang JM. Molecular effects of Genistein on estrogen receptor mediated pathways[J]. Carcinogenesis, 1996,17 (2) :271- 275.
  • 6Nguyen DT,Hernandez-Montes E,Vauzour D,et al. The intracellular Genistein metabolite 5,7,3' ,4'-tetrahydroxyisoflavone mediates G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling pathway[J]. Free Radic Biol Med, 2006,41 (8) : 1225-1239.
  • 7Fioravanti L,Cappelletti VE,Miodini P,et al. Genistein in the control of breast cancer cell growth:insights into the mechanism of action in vitro [J]. Cancer Lett, 1998,130(1-2) : 143-152.
  • 8Brown n DM,Azios NG, Fuqua BK,et al. Flavonoid effects relevant to caneer[J]. J Nutr, 2002,132 ( 11 ) : 3482S-3489S.
  • 9Katdare M ,Osborne M ,Telang NT. Soy isofiavone genistein modulates cell cycle progression and induces apoptosis in HER-2/neu oncogene ex- pressing human breast epithelial cells[J]. Int J Onco1,2002,21 (4) : 809- 815.
  • 10Welcsh Pl,,l e MK,Gunzalez-Hernandez RM,et al. BRCAI transcription- ally regulates genes involved in breast tumorigenesis[J]. PNAS,2002,99 ( 11 ) : 7560-7565.

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