摘要
目的研究微管微丝交连因子1(MACF1)在胶质母细胞瘤应对TMZ刺激中的作用。方法替莫唑胺刺激人类胶质母细胞瘤细胞系U87细胞后,通过Western blot、RT-PCR和免疫荧光检测其蛋白表达和细胞内定位。通过RNA干扰技术干扰MACF1的表达。通过裸鼠皮下成瘤和免疫组化检测在活体中TMZ刺激后胶质母细胞瘤中MACF1的表达。结果在体外培养和体内成瘤中均发现替莫唑胺刺激后胶质母细胞瘤MACF1的表达上调(差异约2倍),胞内分布改变(P<0.01)。敲除MACF1表达的胶质母细胞瘤细胞在TMZ刺激后其增殖能力下调约45%(P<0.01)。替莫唑胺诱导胶质母细胞瘤MACF1表达上调的同时,其细胞骨架发生重组。结论 MACF1可能成为胶质母细胞瘤治疗的一个潜在靶点。
Objective To investigate the role of microtubule-actin crosslinking factor 1 （MACF1） in the response of glioma cells to temozolomide （TMZ）.Methods TMZ was applied to a human gliomablastoma cell line （U87） and changes in the protein expression and cellular localization were determined with Western blot,RT-PCR,and immunofluorescence.The responses of the cells with MACF1 expression knockdown by RNA interference to TMZ were assessed.TMZ-induced effects on MACF1 expression were also assessed by immunohistochemistry in a nude mouse model bearing human glioblastoma xenografts.Results TMZ resulted in significantly increased MACF1 expression （by about 2 folds） and changes in its localization in the gliomablastoma cells both in vitro and in vivo （P〈0.01）.Knockdown of MACF1 reduced the proliferation （by 45%） of human glioma cell lines treated with TMZ （P〈0.01）.TMZ-induced changes in MACF1 expression was accompanied by cytoskeletal rearrangement.Conclusion MACF1 may be a potential therapeutic target for glioblastoma.
作者
谢思迪
陈子阳
王海
何敏毅
陆云涛
雷炳喜
李和珍
刘亚伟
漆松涛
XIE Sidi CHEN Ziyang WANG Hai HE Minyi LU Yuntao LEI Bingxi LI Hezhen LIU Yawei QI Songtao(Department of Neurosurgery, Nanfang Glioma Center 3Center for Clinical Medical Education, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Chin 2Department of Neurosurgery, Sixth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511500, Chin Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510000, China Department of Neurosurgery, Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510900, China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2017年第9期1183-1189,共7页
Journal of Southern Medical University
基金
国家自然基金(81372692
81302229
81472315)
广东省自然科学基金(2014A030313167)
高校博士学科点专项科研基金(20134433120014)
国家临床重点专科建设项目经费资助~~
关键词
细胞骨架
微管微丝交连因子1
胶质母细胞瘤
替莫唑胺
cytoskeleton rearrangement
microtubule-actin crosslinking factor 1
temozolomide
glioblastoma multiforme
