title: HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway.
abstract: In the present study, we examined the mechanisms of oxaliplatin-induced drug resistance in human colorectal cancer cell lines HT29 and HCT116. Our results demonstrate a significant autophagy expression in CRC cells after an oxaliplatin treatment. Administration of oxaliplatin to human CRC cells significantly enhanced the expression of HMGB1, which regulated the autophagy response and negatively regulate the cell apoptosis. Moreover, a decreased oxaliplatin -induced autophagy response and an increased apoptosis level were detected in stable CRC cells harboring HMGB1 shRNA. Then we noted that HMGB1 significantly induced extracellular signal-regulated kinase (ERK)/Extracellular signal-regulated kinase kinase (MEK) phosphorylation. Taken together, these data suggest that HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway.
authors.affiliation: a Department of Anorectal Surgery; The First People's Hospital of Yunnan Province; Kunhua Hospital Affiliated to Kunming University of Science and Technology ; Kunming , Yunnan , China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Liu
authors.forename: Zhenyong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xinju
authors.initials: X
authors.lastname: Chen
authors.forename: Shikui
authors.initials: S
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Lei
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Bi
authors.forename: Kunhua
authors.initials: K
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D045325:HCT116 Cells; D024243:HMGB1 Protein / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 3-MA, 3-methyladenosine; 5-FU, 5-fluorouracil; CCK8, Cell Counting Kit-8; CRC, Colorectal cancer; ERK, extracellular signal-regulated kinase; HMGB1; HMGB1, High–mobility group box 1 protein; MEK, extracellular signal-regulated kinase kinase; MEK/ERK pathway; apoptosis; autophagy; colorectal cancer; oxaliplatin; shRNA, short hairpin RNA