Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray

doi:10.3892/or.2018.6322

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray
	Lin, Jing 4; Zuo, Jianling 5; Cui, Yong 6; Song, Chaoli 4; Wu, Xiaojun 9; Feng, Huaizhi 3; Li, Jian 2; Li, Shuo 3; Xu, Qinian 5; Wei, Wenxin 1
刊名	ONCOLOGY REPORTS
	2018-05
卷号	39 期号:5 页码:2333-2341
关键词	acquired chemoresistance cancer stemness protein microarray glioma SRC family kinases
ISSN号	1021-335X
DOI	10.3892/or.2018.6322
文献子类	Article
英文摘要	Acquired chemoresistance refers to tumor cells gradually losing their sensitivity to anticancer drugs during the course of treatment, resulting in tumor progression or recurrence. This phenomenon, which has deleterious outcomes for the patient, has long been observed in patients with glioblastoma receiving temozolomide (TMZ)-based radiochemotherapy. Currently, the mechanisms for acquired TMZ chemoresistance are not fully understood. In the present study, a TMZ-resistant cell line U251R with a 4-fold 50% inhibition concentration compared with its TMZ-sensitive parent cell line was isolated by incremental long-time TMZ treatment in the human glioblastoma cell line U251. Fluorescence-activated cell sorting analysis indicated G2/M arrest and a lower proportion of cells in the S phase, accompanied by a decreased apoptosis rate in the U251R cell line compared with the parental U251 cell line. In addition, a sphere-formation assay indicated an increased self-renewal capacity in U251R cells. Furthermore, a high-throughput protein microarray unveiled more than 200 differentially expressed proteins as potential molecular targets accounting for acquired TMZ resistance. Subsequent bioinformatics analysis illustrated the molecular and signaling networks and revealed the central role of SRC. Immunoblotting and reverse-transcription quantitative polymerase chain reaction analysis further confirmed the expressional upregulation of SRC family kinases. Moreover, SRC knockdown led to partial reversal of TMZ resistance in the U251R cell line and sensitization in the U373 cell line. These data helped to develop a comprehensive understanding of survival strategies, particularly with respect to pro-stemness regulation, which could be potential targets for overcoming TMZ resistance.
资助项目	National Natural Science Foundation[81302187] ; National Natural Science Foundation[81702944] ; Ministry of Health of the People's Liberation Army[CWS14C063] ; State Key Laboratory of Drug Research[SIMM1705KF-10] ; Medical Project of Sichuan Province Medical Association[S15005] ; Special Presidential Foundation of the General Hospital of Jinan Military Command[2016BS04]
WOS关键词	MALIGNANT GLIOMA ; CANCER-CELLS ; MESENCHYMAL TRANSITION ; AKT ACTIVATION ; CHEMORESISTANCE ; SENSITIVITY ; KINASES ; GROWTH ; SRC ; INHIBITION
WOS研究方向	Oncology
语种	英语
出版者	SPANDIDOS PUBL LTD
WOS记录号	WOS:000429205600031
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279790]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Qiu, Guanzhong; He, Hua
作者单位	1.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China 2.452 Hosp Western Air Force, Dept Urol, Chengdu 610021, Sichuan, Peoples R China; 3.452 Hosp Western Air Force, Dept Nutr, Chengdu 610021, Sichuan, Peoples R China; 4.452 Hosp Western Air Force, Dept Neurosurg, Chengdu 610021, Sichuan, Peoples R China; 5.Soochow Univ, Affiliated Hosp 1, Brain Res Lab, Suzhou 215006, Jiangsu, Peoples R China; 6.Peoples Liberat Army, Hosp 411, Dept Neurosurg, Shanghai 200081, Peoples R China; 7.Jinan Mil Command, Dept Neurosurg, Gen Hosp, 25 Shifan Rd, Jinan 250031, Shandong, Peoples R China; 8.Chinese Acad Sci, Shanghai Inst Mat Medica, State Key Lab Drug Res, Beijing 201203, Peoples R China; 9.Second Mil Med Univ, Changzheng Hosp, Dept Neurosurg, 415 Fengyang Rd, Shanghai 200003, Peoples R China;
推荐引用方式 GB/T 7714	Lin, Jing,Zuo, Jianling,Cui, Yong,et al. Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray[J]. ONCOLOGY REPORTS,2018,39(5):2333-2341.
APA	Lin, Jing.,Zuo, Jianling.,Cui, Yong.,Song, Chaoli.,Wu, Xiaojun.,...&He, Hua.(2018).Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray.ONCOLOGY REPORTS,39(5),2333-2341.
MLA	Lin, Jing,et al."Characterizing the molecular mechanisms of acquired temozolomide resistance in the U251 glioblastoma cell line by protein microarray".ONCOLOGY REPORTS 39.5(2018):2333-2341.