雌激素受体阴性乳腺癌中,癌细胞的活化增殖依赖于非雌激素激活通路。传统内分泌治疗因耐药而疗效低下。通过肿瘤细胞相关信号激活通路,从蛋白和基因层面阻断肿瘤细胞的活化和增殖;也可以阻断相关耐药基因和蛋白,使得传统内分泌治疗有效。作者对雌激素受体阴性乳腺癌多药耐药的机制通路及诱导乳腺癌细胞凋亡和自噬等方面的近年研究进展进行了综述。

[1] BARTOSIEWICZ D,KRASOWSK A.Inhibitors of ABC transporters and biophysical methods to study their activity[J].Z Naturforsch C,2009,64(5-6):454-458.
[2] CHEKHUN V F,LUKYANOVA N Y,KOVALCHUK O,et al.Epigenetic profiling of multidrug-resistant human MCF-7 breast adenocarcinoma cells reveals novel hyper- and hypomethylated targets[J].Mol Cancer Ther,2007,6(3):1089-1098.
[3] UGGLA B,STHL E,WGSTER D,et al.BCRP mRNA expression v.clinical outcome in 40 adult AML patients[J].Leuk Res,2005,29(2):141-146.
[4] 敬静,郑鸿,王静.丹参酮ⅡA对人ER阴性乳腺癌细胞的生长抑制和多耐药逆转作用[J].四川大学学报:医学版,2007,38(3):391-395.
[5] TOYODA Y,HAGIYA Y,ADACHI T,et al.MRP class of human ATP binding cassette (ABC) transporters:historical background and new research directions[J].Xenbobiotica,2008,38(7-8):833-862.
[6] OH A S,LORANT L A,HOLLOWAY J N,et al.Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer cells[J].Mol Endocrinol,2001,158,15(8):1344-1359.
[7] RIGGINS R B,THOMAS K S,TA H Q,et al.Physical and functional interactions between Cas and c-Src induce tamoxifen resistance of breast cancer cells through pathways involving epidermal growth factor receptor and signal transducer and activator of transcription 5b[J].Cancer Res,2006,66(14):7007-7015.
[8] KOVALCHUK O,FILKOWSKI J,MESERVY J,et al.Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin[J].Mol Cancer Ther,2008,7(7):2152-2159.
[9] GRADILONE A,NASO G,RAIMONDI C,et al.Circulating tumor cells (CTCs) in metastatic breast cancer (MBC):prognosis,drug resistance and phenotypic characterization[J].Ann Oncol,2011,22(1):86-92.
[10] HUTCHESON I R,KNOWLDEN J M,HISCOX S E.Heregulin betal drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells[J].Breast Cancer Res,2007,9(4):R50.
[11] LAI C J,BAO R,TAO X,et al.CUDC-101,a multitargeted inhibitor of histone deacetylase,epidermal growth factor receptor,and human epidermal growth factor receptor 2,exerts potent anticancer activity[J].Cancer Res 2010,70(9):3647-3656.
[12] DAVIES G F,ROSS A R,ARNASON T G,et al.Troglitazone inhibits histone deacetylase activity in breast cancer cells[J].Cancer Letters,2010,288(2):236-250.
[13] VANDERLAAG K,SU Y,FRANKEL A E,et al.1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induce autophagic cell death in estrogen receptor negative breast cancer[J].BMC Cancer,2010,10:669.
[14] SINHA S,ROY S,REDDY B S,et al.A lipid-modified estrogen derivative that treats breast cancer independent of estrogen receptor expression through simultaneous induction of autophagy and apoptosis[J].Mol Cancer Res,2011,9(3):364-374.
[15] LEE C W,RASKETT C M,PRUDOVSKY I,et al.Molecular dependence of estrogen receptor-negative breast cancer on a notch-survivin signaling axis[J].Cancer Res,2008,68(13):5273-5281.