福建医科大学学报
福建醫科大學學報
복건의과대학학보
JOURNAL OF FUJIAN MEDICAL UNIVERSITY
2015年
1期
1-6
,共6页
柯春林%林帅%田崛%柯方%吴丽贤
柯春林%林帥%田崛%柯方%吳麗賢
가춘림%림수%전굴%가방%오려현
新生霉素%蛋白质类%H sp90热休克蛋白质类%热休克蛋白质类%分子监控蛋白类%乳腺肿瘤/细胞学
新生黴素%蛋白質類%H sp90熱休剋蛋白質類%熱休剋蛋白質類%分子鑑控蛋白類%乳腺腫瘤/細胞學
신생매소%단백질류%H sp90열휴극단백질류%열휴극단백질류%분자감공단백류%유선종류/세포학
novobiocin%proteins%Hsp90 heat-shock proteins%heat-shock proteins%molecular chaperones%breast neoplasms/cytology
目的：研究新生霉素衍生物FM‐NOV17对乳腺癌Skbr3细胞的作用，并探讨该作用是否与其干扰热休克蛋白90（Hsp90）分子伴侣的功能从而促进Her2降解有关。方法用蛋白免疫印迹法检测Her2的含量，采用免疫共沉淀的方法研究FM‐NOV17对乳腺癌细胞 Hsp90分子伴侣功能的影响。用免疫共沉淀的方法将 Her2与其分子伴侣复合物沉淀下来，用免疫印迹法检测沉淀物中与 Her2结合的 Hsp90和辅伴侣 Hsp70含量的变化。结果 FM‐NOV17能降低乳腺癌细胞Skbr3中Her2的蛋白水平，FM‐NOV17使Her2与Hsp90和Hsp70的结合减少，降低Her2蛋白水平，诱导细胞周期阻滞和凋亡。结论 FM‐NOV17通过干扰 Hsp90伴侣功能，减少Her2与Hsp90和辅伴侣的结合，降低 Her2蛋白量，最终抑制乳腺癌细胞增殖。
目的：研究新生黴素衍生物FM‐NOV17對乳腺癌Skbr3細胞的作用，併探討該作用是否與其榦擾熱休剋蛋白90（Hsp90）分子伴侶的功能從而促進Her2降解有關。方法用蛋白免疫印跡法檢測Her2的含量，採用免疫共沉澱的方法研究FM‐NOV17對乳腺癌細胞 Hsp90分子伴侶功能的影響。用免疫共沉澱的方法將 Her2與其分子伴侶複閤物沉澱下來，用免疫印跡法檢測沉澱物中與 Her2結閤的 Hsp90和輔伴侶 Hsp70含量的變化。結果 FM‐NOV17能降低乳腺癌細胞Skbr3中Her2的蛋白水平，FM‐NOV17使Her2與Hsp90和Hsp70的結閤減少，降低Her2蛋白水平，誘導細胞週期阻滯和凋亡。結論 FM‐NOV17通過榦擾 Hsp90伴侶功能，減少Her2與Hsp90和輔伴侶的結閤，降低 Her2蛋白量，最終抑製乳腺癌細胞增殖。
목적：연구신생매소연생물FM‐NOV17대유선암Skbr3세포적작용，병탐토해작용시부여기간우열휴극단백90（Hsp90）분자반려적공능종이촉진Her2강해유관。방법용단백면역인적법검측Her2적함량，채용면역공침정적방법연구FM‐NOV17대유선암세포 Hsp90분자반려공능적영향。용면역공침정적방법장 Her2여기분자반려복합물침정하래，용면역인적법검측침정물중여 Her2결합적 Hsp90화보반려 Hsp70함량적변화。결과 FM‐NOV17능강저유선암세포Skbr3중Her2적단백수평，FM‐NOV17사Her2여Hsp90화Hsp70적결합감소，강저Her2단백수평，유도세포주기조체화조망。결론 FM‐NOV17통과간우 Hsp90반려공능，감소Her2여Hsp90화보반려적결합，강저 Her2단백량，최종억제유선암세포증식。
Objective To confirm the effects of FM‐NOV17 ,one of novobiocin derivatives ,on breast cancer cells (Skbr3) ,and to study the relationship between these effects and the molecular chaper‐one functions of heat shock protein 90 (Hsp90) . Methods The quantity of Her2 protein was determined by Western‐blot . Molecular chaperone functions of Hsp90 on breast cancer cells were measured by coim‐munoprecipitation . After the co‐immunoprecipitation of Her2 and its molecular chaperones ,the immuno‐precipitate was then subjected to Western‐blot analysis with anti‐Her2 to study changes in quantity of anti‐Hsp90 ,or anti‐Hsp70 mAb . Results An exposure of Skbr3 cells to FM‐NOV17 led to down‐regulation of intracellular Her2 protein levels . FM‐NOV17 treatment also decreased the binding of Her2 with Hsp90 and Hsp70 . Consequently ,apoptosis and cell cycle arrest were induced . Conclusions These studies demonstrate that the activities of FM‐NOV17 might inhibit breast cancer cells through the disrup‐tion of Hsp90 chaperon function ,which results in disruption of the binding of Her2 to Hsp90 and cochap‐erons and the level of Her2 protein . That may be an important mechanism ,by which FM‐NOV17 medi‐ates its effects on breast cancer cells .
