title: Expression of dynein, cytoplasmic 2, heavy chain 1 (DHC2) associated with glioblastoma cell resistance to temozolomide.
abstract: Temozolomide (TMZ) is the main chemotherapeutic drug utilized for the treatment of glioblastoma multiforme (GMB), however, drug resistance often leads to tumor recurrence and poor outcomes. GMB cell lines were treated with TMZ for up to two weeks and then subjected to proteomics analysis to identify the underlying molecular pathology that is associated with TMZ resistance. Proteomics data showed that TMZ altered expression of proteins that related to cytoskeleton structure and function, such as DHC2 and KIF2B. qRT-PCR and immunofluorescence were used to verify expression of DHC2 and KIF2B in these cells. Immunohistochemistry was used to verify expression of these two proteins in xenografts of a nude mouse model, and ex vivo GBM tissue samples. Their expression was knocked down using siRNA to confirm their role in the regulation of GBM cell sensitivity to TMZ. Knockdown of DHC2 expression enhanced sensitivity of U87 cells to TMZ treatment. Ex vivo data showed that DHC2 expression in GBM tissue samples was associated with tumor recurrence after TMZ chemotherapy. These results indicated cytoskeleton related protein DHC2 reduced sensitivity of GBM cells to TMZ treatment. Further studies should assess DHC2 as a novel target in GBM for TMZ combination treatment.
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hezhen
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Minyi
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515,China.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Bingxi
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Nanfang Neurosurgery Research Institution, Nanfang hospital, Southern Medical University, Guangzhou 510515,China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056445:Cytoplasmic Dyneins / Q000096:biosynthesis*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004351:Drug Resistance; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000096:biosynthesis; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009457:Neuroglia / Q000187:drug effects*; D020543:Proteome / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; C099883:DYNC2H1 protein, human; D020543:Proteome; D003606:Dacarbazine; C523507:KIF2B protein, human; D056445:Cytoplasmic Dyneins; D016547:Kinesins; D000077204:Temozolomide