p75NTR对乳腺癌耐药细胞MDA-MB-231/ADR耐药及细胞周期的影响  

Effects of neurotrophin receptor p75NTR on drug resistance and cell cycle in breast cancer resistant cell line MDA-MB-231/ADR

作　　者：邓晓芳[1] 徐岗[2] 何利珍[3] 

机构地区：[1]广州医科大学附属肿瘤医院内二科,广东广州510095 [2]广州医科大学附属肿瘤医院胸外科,广东广州510095 [3]广州医科大学附属肿瘤医院病理科,广东广州510095

出　　处：《海南医学》2017年第15期2414-2417,共4页Hainan Medical Journal

基　　金：广东省卫生计生委医学科研基金(编号:B2016070);广州医科大学科研资助项目(编号:2015C42)

摘　　要：目的探讨神经营养因子受体(p75NTR)对乳腺癌耐药细胞MDA-MB-231/ADR化疗耐药性及细胞周期的影响。方法采用CCK-8法检测转染p75NTR及p75NTR-siRNA后乳腺癌耐药细胞系MDA-MB-231/ADR对耐药的影响;FCM检测转染p75NTR及p75NTR-siRNA的乳腺癌及耐药细胞的细胞周期分布及细胞凋亡的影响。结果过表达p75NTR可有效增强MDA-MB-231/ADR细胞对ADM、G_1EM和OXA的耐药性(P<0.05);抑制p75NTR的表达可抑制MDA-MB-231/ADR细胞对ADM、G_1EM和OXA的耐药性(P<0.05)。转染pc DNA3.1-p75NTR后,MDA-MB-231/ADR-p75NTR细胞的细胞周期阻滞于G_(10)/G_(11)期,G_(10)/G_(11)期细胞增至(61.12±1.89)%,S期细胞减至(32.76±0.23)%,凋亡率减至(16.83±1.29)%,差异有统计学意义(P<0.05);转染p75NTR-siRNA后MDA-MB-231/ADR-p75NTRsi1细胞的细胞周期于G_(10)/G_(11)期减至(39.26±1.31)%,S期细胞增至(52.88±1.74)%,凋亡率增至(21.49±1.41)%,差异有统计学意义(P<0.05)。结论过表达p75NTR能够使乳腺癌耐药细胞MDA-MB-231/ADR细胞周期阻滞于G_(10)/G_(11)期,促进细胞存活,抑制其凋亡,降低MDA-MB-231/ADR细胞对化疗药物的敏感性而促进其多药耐药性。Objective To investigate the effects of neurotrophin receptor p75NTR on drug resistance and cell cycle in breast cancer resistant cell line MDA-MB-231/ADR. Methods The multi-drug resistance effects of the overexpression and knock-down p75NTR on breast cancer cell line MDA-MB-231/ADR were detected by CCK-8 assay. Flow cytometry（FCM） was used to detect the effects of the overexpression and knock-down of p75NTR on the cell cycles distribution and apoptosis. Results The overexpression of p75NTR can effectively enhance the resistance of MDA-MB-231/ADR cells to Doxorubicin（ADM）, Gentamicin（GEM） and Oxacillin（OXA）（P〈0.05）. The inhibition of p75NTR expression can increase the sensitivity of MDA-MB-231/ADR cells to ADM, GEM and OXA（P〈0.05）. After the transfection of pc DNA3.1-p75NTR, MDA-MB-231/ADR-p75NTR cell cycle arrested in G0/G1 phase. The number of cells in G0/G1 phase increased to （61.12±1.89）% and those in S phase decreased to （32.76±0.23）% . Additionally, apoptosis rate in S phase decreased to （16.83 ± 1.29）% , P〈0.05. After the transfection of p75NTR-siRNA, the number of cells in G0/G1 phase decreased to （39.26±1.31）% and those in S phase increased to （52.88±1.74）% . And apoptosis rate in S phase increased to （21.49±1.41）% （P〈0.05）. Conclusion The overexpression of p75NTR can make MDA-MB-231/ADR cell cycle arrest in G0/G1 phase, promote cell survival, inhibit the apoptosis, reduce the sensitivity to chemotherapeutic drugs and promote its multidrug resistance.

关 键 词：乳腺癌 神经营养因子受体 多药耐药 细胞周期 

分 类 号：R737.9[医药卫生—肿瘤]