title: Cbl-b enhances sensitivity to 5-fluorouracil via EGFR- and mitochondria-mediated pathways in gastric cancer cells.
abstract: 5-Fluorouracil (5-FU) is an essential component of anticancer chemotherapy against gastric cancer. However, the response rate of single drug is still limited. The ubiquitin ligase Cbl-b is a negative regulator of growth factor receptor signaling and is involved in the suppression of cancer cell proliferation. However, whether Cbl-b could affect 5-FU sensitivity remains unclear. The present study showed that Cbl-b knockdown caused higher proliferation concomitant with the decrease of apoptosis induced by 5-FU treatment in gastric cancer cell. Further mechanism investigation demonstrated that Cbl-b knockdown caused significant increase of phosphorylation of EGFR, ERK and Akt, decrease of mitochondrial membrane potential, and increase of expression ratio of Bcl-2/Bax. These results suggest that Cbl-b enhances sensitivity to 5-FU via EGFR- and mitochondria-mediated pathways in gastric cancer cells.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Yanju
authors.initials: Y
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinglei
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China. ypliu@mail.cmu.edu.cn.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China. cmuquxiujuan@gmail.com.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005472:Fluorouracil / Q000633:toxicity*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005472:Fluorouracil