title: B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway.
abstract: B7-H3, a member of the B7 family, has been reported to be highly expressed in colorectal cancer and is associated with poor prognosis and overall survival. In this study, we found that overexpression of B7-H3 protected SW80 and HCT8 cells from 5-fluorouracil (5-FU) using CCK-8 assays by inducing resistance to 5-FU chemotherapy. Further investigation has revealed elevated expression of thymidylate synthase (TS) and upregulation of the PI3-kinase (PI3K)/Akt pathway in B7-H3 overexpressing cells. The effects of B7-H3 on activation of the PI3K/Akt pathway and elevation of TS expression could be blocked by LY294002, a specific inhibitor of the PI3K signaling pathway. These results implied that B7-H3 can induce colorectal cancer cell resistance to 5-FU by increasing TS expression and PI3K/Akt/TS signaling and plays an important role during these processes. This study provides more proof concerning the non-immunology effect of B7 molecules, a reminder that both co-stimulatory or inhibitory effects and non-immunology effects should be devoted equal attention.
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: ZhiHui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China. huadong@csco.org.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D060887:B7 Antigens / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human; D012333:RNA, Messenger; D013940:Thymidylate Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil
keywords: 5-FU resistance; B7 molecules; B7-H3; Colon cancer; PI3K-Akt; Thymidylate synthase