title: Potential biomarkers for sensitivity of gallbladder cancer cells to gemcitabine.
abstract: Gemcitabine (Gem)-based chemotherapies are the main therapeutic regimens for patients with unresectable advanced or metastatic gallbladder cancer (GBC). However, the modest ORR and mild benefit on survival demonstrates the need for finding biomarkers for sensitivity to Gem and hence improving the therapy. In present work, two GBC cell lines with vast difference in sensitivity to Gem were subjected to DNA microarray analysis. Dramatic expression difference was found in protein kinase A signaling, P2Y purigenic receptor signaling, ErbB signaling and p70S6K signaling. Predicted low expression of KRAS and inactivation of AKT/ERK signaling in Gem-resistant GBC cells was validated by quantitative PCR and immunoblotting, respectively. However, p70S6K, p38MAPK and NF-κB signaling was probably activated in Gem-resistant GBC cells, which deserves further investigation in more GBC cell lines and tissues. Our work provides potential pathway signatures for Gem sensitivity of GBC patients.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Huo-Jian
authors.initials: HJ
authors.lastname: Shen
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Shi
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to The School of Medicine, Shanghai Jiaotong University Shanghai, 200127, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Ji
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: AKT signaling; DNA microarray analysis; ERK signaling; Gallbladder cancer; KRAS; NF-κB; gemcitabine; p38MAPK; p70S6K