摘要
Abstract
Objective To investigate the mechanisms of interleukin - 1 receptor - associated kinase 1(IRAK1)in the treatment for breast cancer patients with resistance to paclitaxel. Methods From May 2013 to September 2015,the Department of Oncology,the First Affiliated Hospital of Gannan Medical University,collected breast tissues of 16 control female (breast fibrous tumor)and those of patients with differential subtypes of breast cancer,including 38 Basal-like breast cancer,25 Luminal-A breast cancer,31 Luminal-B breast cancer,31 HER2 overexpressed breast cancer,and 58 TNBC breast cancer. The relative expression level of IRAK1 mRNA in controls and different breast cancer patients were measured by real - time PCR. The level of inflammatory cytokines such as IL-6,IL-8,CXCL-1 were detected by ELISA. Breast cancer cell lines (HMEC, MCF7, MB415, MB436, MB468, BT549 and SUM159 ) were cultured. Through low concentration gradient increment combined with large dose intermittent shock,breast cancer cell lines obtained resistance to paclitaxel. The relative expression level of IRAK1 mRNA of various breast cancer cell lines with resistance to paclitaxel and without paclitaxel treatment were measured by real - time PCR. When breast cancer cell lines with resistance to paclitaxel were transfected by shRNA or blank sequence NC-shRNA,real - time PCR was performed to detect the relative expression level of proliferation - associated genes such as Cyclin D1 ,PCNA and Cyclin A,that of apoptosis - related genes such as p53,c-myc,Bcl-2 and c-erb-2,and that of migration - related genes such as Cullin 1,Bcl-6 and KLF6. ALDEFLUOR testing was used to detect the activity of aldehyde dehydrogenase(ALDH). Results The relative expression level of IRAK1 mRNA in various subtypes of paclitaxel - resistant breast cancer patients was much higher than that of the non - resistant patients( P < 0. 05). The relative expression level of IRAK1 mRNA in paclitaxel - resistant TNBC was higher than that of other subtypes of paclitaxel - resistant patients(P < 0. 05). The differences in the expression levels of IL-6,IL-8 and CXCL-1 between the controls and the various paclitaxel - resistant breast cancer patients showed statistical significance( P < 0. 05). The relative expression level of IRAK1 mRNA in various subtypes of paclitaxel - resistant breast cancer cell lines was higher than that of the cell lines without paclitaxel treatment(P <0. 05). Compared with the paclitaxel - resistant breast cancer cell lines with NC-shRNA transfection,the various paclitaxel -resistant breast cancer cell lines with shRNA tranfection had lower Cyclin D1 ,PCNA,Cyclin A,Cullin 1 and Bcl-6 relative expression levels and lower ALDH activity,but higher p53,c-myc,Bcl-2,c-erb-2 and KLF6 relative expression levels(P <0. 05). Conclusion IRAK1 plays an essential role in paclitaxel - resistance breast cancer cells especially in TNBC. When the expression of IRAK1 was inhibited,the proliferation and migratory ability could be remarkably decreased inducing abundant breast cancer cell apoptosis,so IRAK1 inhibitors could be used in breast cancer therapy especially in TNBC.关键词
乳腺肿瘤/抗药性,肿瘤/白介素1受体相关激酶类/细胞增殖/细胞凋亡Key words
Breast neoplasms/Drug resistance,neoplasm/Interleukin - 1 receptor - associated kinases/Cell proliferation/Apoptosis分类
医药卫生
