Shh和Gli-1在人乳腺癌MCF-7耐药细胞株中的表达及意义  

Expression and significance of Shh and Gli-1 in drug-resistant cell strain of human breast cancer MCF-7

作　　者：刘瑞娟[1] 臧传鑫 孙月[3] 韩娜娜[1] 孙长岗[1] 

机构地区：[1]潍坊市中医院肿瘤中心,山东潍坊261041 [2]山东中医药大学中医学院,250355 [3]潍坊医学院研究生院,261053

出　　处：《临床肿瘤学杂志》2016年第4期289-292,共4页Chinese Clinical Oncology

基　　金：国家自然科学基金资助项目(81273987;81473513)

摘　　要：目的研究Shh和Gli-1在人乳腺癌耐药株中的表达情况,探讨Hedgehog信号通路与乳腺癌耐药的关系。方法高浓度间歇诱导法建立人乳腺癌耐药细胞株MCF-7/PTX,MTT法检测紫杉醇(PTX)对MCF-7与MCF-7/PTX细胞的半数抑制浓度(IC_(50))。实时定量PCR(QPCR)检测MCF-7、MCF-7/PTX细胞中Shh、Gli-1 mRNA的表达。Western blotting检测MCF-7、MCF-7/PTX细胞中Shh、Gli-1蛋白的表达。结果 PTX对MCF-7细胞的IC_(50)为(0.10±0.02)mg/L,对MCF-7/PTX细胞的IC_(50)为(5.30±0.01)mg/L;耐药指数为53.0。Shh mRNA在MCF-7、MCF-7/PTX细胞中的表达量分别为0.78±0.12和1.45±0.56(P<0.01);Gli-1 mRNA在MCF-7、MCF-7/PTX细胞中的表达量分别为1.86±0.02和3.56±0.26(P<0.01)。Shh蛋白在MCF-7、MCF-7/PTX细胞中的表达量分别为0.58±0.06和1.03±0.22(P<0.01);Gli-1蛋白在MCF-7、MCF-7/PTX细胞中的表达量分别为1.17±0.12和2.78±0.09(P<0.01)。结论人乳腺癌耐药细胞株MCF-7/PTX高表达Shh、Gli-1,化疗药物可能通过上调Hedgehog信号通路相关蛋白及基因介导乳腺癌耐药,针对该信号通路的靶向治疗将是克服乳腺癌耐药的一个新的选择。Objective To investigate the expression of Shh,Gli-1 in human breast cancer resistant cell line and discuss the relationship between Hedgehog signaling pathway and drug resistance of breast cancer. Methods Drug-resistant strains of human breast cancer MCF-7 was established by high concentration intermittent induction. Paclitaxel（ PTX） to half maximal inhibitory concentration（ IC_（50）） on MCF-7 and MCF-7 /PTX cells was determined by MTT. QPCR was used to detect the mRNA expression of Shh,Gli-1 in MCF-7 and MCF-7 / PTX cells. Protein expression of Shh,Gli-1 in MCF-7 and MCF-7 / PTX cells was detected by Western blotting. Results IC_（50） of PTX for MCF-7 cells was（ 0. 10 ＋ 0. 02） mg / L,and for MCF-7 / PTX cell was（ 5. 30 ＋ 0. 01） mg / L. The drug resistance index was 53. 0. The expression of Shh mRNA in MCF-7 and MCF-7 / PTX cells was 0. 78 ± 0. 12 and 1. 45 ± 0. 56（ P 0. 01）,and the expression levels of Gli-1 mRNA was 1. 86 ± 0. 02 and 3. 56 ± 0. 26（ P〈 0. 01）. The expression level of Shh protein in MCF-7 and MCF-7 / PTX cells was 0. 58 ± 0. 06 and 1. 03 ± 0. 22（ P〈 0. 01）. Gli-1 protein expression in MCF-7 and MCF-7 / PTX cells was 1. 17 ± 0. 12 and 2. 78 ± 0. 09（ P〈 0. 01）. Conclusion Shh,Gli-1 are highly expressed in MCF-7 / PTX cells,indicating that chemotherapy may guide drug resistance of breast cancer by up-regulating the protein and gene of hedgehog signaling pathway. The target to hedgehog signaling pathway may be a new direction to overcome drug resistance.

关 键 词：乳腺癌 耐药细胞株 HEDGEHOG信号通路 SHH Gli-1 

分 类 号：R737.9[医药卫生—肿瘤]