title: HES 1 is essential for chemoresistance induced by stellate cells and is associated with poor prognosis in pancreatic cancer.
abstract: The role of pancreatic stellate cells (PSCs) has been established in many studies. However, the potential mechanism for the chemoresistance induced by PSCs has not been fully elucidated. In the present study, human pancreatic cancer cell lines were directly or indirectly co-cultured with PSCs. The inhibition rate and IC50 values were assessed to determine the ability of chemoresistance. RT-PCR and western blot analysis were used to evaluate Hes 1 and Jagged 1 expression before and after co-culture with PSCs. To determine the relationship between Hes 1 expression and survival in pancreatic cancer patients, Kaplan-Meier survival analysis was performed. PSCs promoted the expression of Hes 1 in both PANC-1 and BxPC-3 cell lines and induced chemoresistance to gemcitabine. A Notch signaling pathway inhibitor (L1790) and Hes 1 siRNA reversed the chemoresistance induced by PSCs. In 72 resected pancreatic cancer patients, high Hes 1 expression was observed in 34 patients with shorter overall and progression-free survival times. In conclusion, Hes 1 is essential for chemoresistance induced by PSCs and is associated with poor prognosis in pancreatic cancer patients. Therapy targeting the Notch signaling pathway may reverse chemoresistance and improve survival in patients with pancreatic cancer.
authors: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors: Feng
authors: F
authors: Cao
authors: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors: Jia
authors: J
authors: Li
authors: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors: Haichen
authors: H
authors: Sun
authors: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors: Shuang
authors: S
authors: Liu
authors: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors: Yeqing
authors: Y
authors: Cui
authors: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors: Fei
authors: F
authors: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000473:pathology / Q000502:physiology*; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000072056:Transcription Factor HES-1; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D051792:Basic Helix-Loop-Helix Proteins; D017077:Culture Media, Conditioned; D003841:Deoxycytidine; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; D000093542:Gemcitabine; C078493:HES1 protein, human