title: Combination of a STAT3 Inhibitor and an mTOR Inhibitor Against a Temozolomide-resistant Glioblastoma Cell Line.
abstract: Temozolomide-resistant (TMZ-R) glioblastoma is very difficult to treat, and a novel approach to overcome resistance is needed.
  
  
  
  The efficacy of a combination treatment of STAT3 inhibitor, STX-0119, with rapamycin was investigated against our established TMZ-resistant U87 cell line.
  
  
  
  The growth-inhibitory effect of the combination treatment was significant against the TMZ-R U87 cell line (IC50: 78 μM for STX-0119, 30.5 μM for rapamycin and 11.3 μM for combination of the two). Western blotting analysis demonstrated that the inhibitory effect of STX-0119 on S6 and 4E-BP1 activation through regulation of YKL-40 expression occurred in addition to the inhibitory effect of rapamycin against the mTOR pathway.
  
  
  
  These results suggest that the STAT3 pathway is associated with the mTOR downstream pathway mediated by YKL-40 protein, and the combination therapy of the STAT3 inhibitor and rapamycin could be worth developing as a novel therapeutic approach against TMZ-resistant relapsed gliomas.
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ashizawa
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kondou
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Nonomura
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugino
authors.affiliation: Cancer Diagnostics Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Nakamasa
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mitsuya
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakasu
authors.affiliation: Office of the President, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan y.akiyama@scchr.jp.|Division of Neurosurgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000071451:Chitinase-3-Like Protein 1 / Q000235:genetics / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D059472:Exome; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D010069:Oxadiazoles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D050796:STAT3 Transcription Factor; C559957:STX-0119; D003606:Dacarbazine; D058570:TOR Serine-Threonine Kinases; D000077204:Temozolomide
keywords: STAT3 inhibitor; glioblastoma; mTOR inhibitor; temozolomide resistance