B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway
B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway
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B7-H3 通过 PI3k-Akt 途径增加胸苷酸合酶表达
DOI：
10.1007/s13277-015-4740-0
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发表时间：
2016-07-01
期刊：
影响因子：
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通讯作者：
Hua, Dong
中科院分区：
文献类型：
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作者：
Jiang, Bo;Liu, Fen;Hua, Dong
B7-H3是B7家族中的一员，已有报道在结直肠癌中高表达，并与不良预后和总生存率有关。在这项研究中，我们发现过表达B7-H3通过诱导5-FU化疗耐药来保护SW80和HCT8细胞免受5-FU的影响。进一步的研究发现，在B7-H3过表达的细胞中，胸苷合成酶(TS)的表达增加，PI3K(PI3K)/Akt通路上调。PI3K信号通路的特异性抑制剂LY294002可阻断B7-H3对PI3K/Akt通路的激活和TS表达的上调。提示B7-H3可通过上调TS表达和PI3K/Akt/TS信号转导途径诱导结直肠癌细胞对5-FU产生耐药，并在此过程中发挥重要作用。这项研究为B7分子的非免疫学效应提供了更多的证据，提醒人们应该对共刺激或抑制效应和非免疫学效应给予同等重视。
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.