title: GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment.
abstract: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms.
  
  
  
  The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. CCK-8 assay detected the cell proliferative capability. Apoptotic cell number was measured by flow cytometry. The transwell assay was used to test the cell invasive capability. DNA damage effect was identified by COMET assay and γH2AX expression.
  
  
  
  Proliferation of tumor cells treated with GANT61 in combination with TMZ was significantly suppressed compared with those treated with either drug used alone. The combination treatment induced a higher rate of apoptosis, DNA damage and reduced the invasive capability of glioma cells. DNA damage repair enzyme MGMT and the Notch1 pathway increased in the cells treated by TMZ treatment. However, GANT61 could abrogated the protein increasing.
  
  
  
  GANT61 sensitizes glioma cells to TMZ treatment by enhancing DNA damage effect, decreasing MGMT expression and the Notch1 pathway.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China.|Neuroscience Institute, Heilongjiang Academy of Medical Sciences, Harbin, 150086, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Daqing LongNan Hospital, Daqing, 163001, China.
authors.forename: Xiuwei
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China. junhezhang2016@163.com.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China. junhezhang2016@163.com.
authors.forename: Junhe
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, 150086, Harbin, People's Republic of China. jcl6688@163.com.|Neuroscience Institute, Heilongjiang Academy of Medical Sciences, Harbin, 150086, China. jcl6688@163.com.|Chinese Glioma Cooperative Group (CGCG), Beijing, 100050, China. jcl6688@163.com.
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D000075746:Zinc Finger Protein Gli2 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: C551027:GANT 61; C400551:GLI1 protein, human; C082593:GLI2 protein, human; C497761:NOTCH1 protein, human; D009687:Nuclear Proteins; D011725:Pyridines; D011743:Pyrimidines; D051881:Receptor, Notch1; D025521:Tumor Suppressor Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: DNA damage; GANT61; Glioma; Hedgehog; Notch1 pathway; O6-methylguanine DNA methyltransferase (MGMT); Temozolomide