摘要
目的探讨热休克蛋白90(Hsp90)抑制剂WK-88-1对人乳腺癌细胞迁移与侵袭能力的影响。方法 MTT实验检测不同浓度的WK-88-1(1. 562 5,3. 125,6. 25,12. 5,25,50μmol/L)对人乳腺癌MDA-MB-231和MCF-7细胞存活率的影响;集落克隆实验检测不同浓度的WK-88-1(0. 1,0. 3,0. 5μmol/L)对人乳腺癌MDA-MB-231和MCF-7细胞集落形成的影响;细胞划痕实验和Transwell小室法检测WK-88-1对人乳腺癌MDA-MB-231和MCF-7细胞迁移和侵袭的影响;免疫印迹法检测WK-88-1对Hsp90顾客蛋白缺氧诱导因子-1α(HIF-1α)和基质金属蛋白酶-9(MMP-9)蛋白表达的影响。结果 WK-88-1具有抑制MDA-MB-231和MCF-7细胞增殖的作用,且呈现浓度和时间依赖性(P<0.05)。MDA-MB-231和MCF-7经不同浓度的WK-88-1处理后,癌细胞的迁移和侵袭能力显著下降(P<0.05)。免疫印迹法结果显示,随着WK-88-1给药浓度(12. 5,25,50μmol/L)的增加,细胞内的HIF-1α和MMP-9蛋白的表达均下调。结论非苯醌格尔德霉素WK-88-1能够显著抑制人乳腺癌细胞迁移与侵袭,其机制可能与下调Hsp90的顾客蛋白HIF-1α和MMP-9有关。
Objective To investigate the effect of WK-88-1,a heat shock protein 90(Hsp90)inhibitor,on the migration and invasion of human breast cancer cells.Methods MTT assay was used to detect the survival rate of human breast cancer MDA-MB-231 and MCF-7 cells after treated with WK-88-1(1.562 5,3.125,6.25,12.5,25,50μmol/L).The effects of WK-88-1(0.1,0.3,0.5μmol/L)on the colony formation of MDA-MB-231 and MCF-7 cells were observed by colony formation experiment.The effect of WK-88-1 on migration and invasion abilities of breast cancer cells were analyzed using wound healing assay and transwell assay.The effects of WK-88-1 on the expression levels of Hsp90 clinent proteins HIF-1αand MMP-9 were detected using Western blotting.Results WK-88-1 exhibited anti-proliferation activities against MDA-MB-231 and MCF-7 cells in a dose-and time-dependent manner(P<0.05).After treatment with different concentrations of WK-88-1,the breast cancer cell migration and invasion abilities significantly decreased(P<0.05).Western blotting results showed that expression levels of HIF-1αand MMP-9 down-regulated by WK-88-1 in a concentration-dependent manner(12.5,25,50μmol/L).Conclusion Non-benzoquinone geldanamycin WK-88-1 significantly inhibit the migration and invasion of human breast cancer cells,which may be related to the down-regulated expression of Hsp90 client proteins HIF-1αand MMP-9.
作者
吴成柱
赵玉茹
李红梅
WU Chengzhu;ZHAO Yuru;LI Hongmei(Department of Medicinal Chemistry,Bengbu Medical College,Bengbu 233030,China;Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals;Department of Chinese Medicine Basic,Bengbu Medical College)
出处
《山西医科大学学报》
CAS
2019年第3期306-312,共7页
Journal of Shanxi Medical University
基金
国家自然科学基金青年项目(81302671)
安徽高校自然科学基金重点项目(KJ2018A0232)
蚌埠医学院科技发展基金资助项目(BYKF1718)
