title: GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo.
abstract: Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the long‑term survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The pro‑survival effect of the insulin‑like growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGF‑IR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dose‑dependent manner. The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo. The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Fazheng
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Hui
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Pei
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Wenke
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Baozhe
authors.initials: B
authors.lastname: Jin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C546191:GSK 1838705A; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D017526:Receptor, IGF Type 1