敲低己糖激酶2(HK2)抑制乳腺癌细胞增殖并降低其对氟尿嘧啶的耐药  

Knockdown of hexokinase 2(HK2) inhibits breast cancer cell proliferation and reduces their resistance to fluorouracil

作　　者：王军华 陶明华 王滕 王孜 肖静 丁巳娟 陈瑞 WANG Junhua;TAO Minghua;WANG Teng;WANG Zi;XIAO Jing;DING Sijuan;CHEN Rui(General Hospital of Tibet Military Region,Lasa 850000,China;University of Tibetan Medicine,Lasa 850000,China)

机构地区：[1]西藏军区总医院核医学科,西藏拉萨850000 [2]西藏藏医药大学藏医药研究所,西藏拉萨850000

出　　处：《细胞与分子免疫学杂志》2021年第8期722-727,共6页Chinese Journal of Cellular and Molecular Immunology

摘　　要：目的研究敲低己糖激酶2(HK2)对乳腺癌细胞增殖、耐药的影响及其机制。方法通过短发夹RNA(shRNA)质粒转染技术构建稳定转染的MDA-MB-231乳腺癌细胞,实时定量PCR及Western blot法检测HK2 mRNA和蛋白水平,噻唑蓝(MTT)法观察HK2对乳腺癌细胞增殖及对5氟脲嘧啶(5-FU)耐药的影响,乳酸试剂盒和细胞外酸化率(ECAR)检测HK2对乳腺癌细胞糖酵解的影响。结果获得稳定低表达HK2的乳腺癌细胞株,HK2 mRNA及蛋白水平均明显降低。敲低HK2后明显抑制乳腺癌细胞的增殖并增强5-FU对乳腺癌细胞的杀伤作用,下调HK2后能够明显抑制乳腺癌细胞乳酸分泌和下调糖酵解基线。结论敲低HK2抑制MDA-MB-231乳腺癌细胞增殖并降低其对5-FU的耐药性。Objective To investigate the effect of knocking down hexokinase 2(HK2) on the proliferation and drug resistance of breast cancer cells and its mechanism. Methods The MDA-MB-231 breast cancer cells were transfected with the short hairpin RNA(shRNA) plasmid. The mRNA and protein levels of HK2 were detected by real-time quantitative PCR and Western blotting, respectively;MTT assay was used to detect the effect of HK2 on the proliferation and 5-fluorouraci(5-FU) resistance of breast cancer cells;Lactate assay and extracellular acidification rate(ECAR) were used to detect the effect of HK2 on the glycolysis of breast cancer cells. Results The breast cancer cell line with stable & low expression of HK2 was obtained, and the mRNA and protein levels of HK2 were significantly reduced. Knockdown of HK2 significantly inhibited the proliferation of breast cancer cells and enhanced the killing effect of 5-FU on them. Down regulation of HK2 significantly inhibited the lactate secretion and lowered the glycolysis baseline in breast cancer cells. Conclusion Knockdown of HK2 inhibits the proliferation of MDA-MB-231 breast cancer cells and reduce their resistance to 5-FU.

关 键 词：乳腺癌细胞 己糖激酶2(HK2) 短发夹RNA(shRNA) 5氟脲嘧啶(5-FU) 糖酵解 

分 类 号：Q279[生物学—细胞生物学] R73-361[医药卫生—肿瘤]