EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73362_C
抗生素；mTOR通路抑制剂；抑制FKBP-12
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总览
雷帕霉素（Rapamycin）是一种大环内酯类抗生素和免疫抑制剂，可抑制哺乳动物雷帕霉素靶蛋白（mTOR）信号传导。它通过与胞浆FK结合蛋白12（FKBP-12）形成复合物发挥作用，而FKBP-12又可直接与mTOR复合物1（mTORC1）结合。其免疫抑制作用是通过抑制对T细胞增殖和激活至关重要的IL-2信号传导来实现的（Gibbons等；Kay等）。雷帕霉素对白色念珠菌和其他真菌具有抗真菌活性（Vézina 等）。
癌症研究
·体外抑制MDA-MB-468人乳腺癌细胞生长，并在小鼠异种移植模型体内抑制肿瘤生长（Akcakanat等）。
·诱导恶性胶质瘤细胞自噬（Takeuchi等）。
细胞类型
癌细胞及细胞系，乳腺细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
应用
抗生素
研究领域
癌症
CAS 编号
53123-88-9
化学式
C₅₁H₇₉NO₁₃
纯度
≥ 95 %
通路
mTOR
靶点
FKBP-12
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
相关材料与文献
技术资料 (3)
文献 (7)
Inhibition of T and B lymphocyte proliferation by rapamycin.
Immunology 1991
Abstract
The immunosuppressive macrolide rapamycin shows marked structural similarity to FK-506,and like FK-506 inhibits the activation of cultured T and B lymphocytes at concentrations as low as 10(-10) M. However,rapamycin blocks T-lymphocyte proliferation at a much later stage than FK-506. It also inhibits human,porcine and murine T- and B-lymphocyte activation by all pathways tested,including pathways which are insensitive to FK-506,such as interleukin-2 (IL-2)-mediated proliferation of IL-2-dependent T-cell lines,activation of human peripheral blood T lymphocytes by phorbol ester and anti-CD28 and activation of murine B lymphocytes by bacterial lipopolysaccharide. Thus these two macrolides that bind competitively to the same major intracellular receptor protein inhibit T- and B-lymphocyte activation by quite distinct mechanisms.
Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.
Blood 2007
Abstract
The mTOR complex 2 (mTORC2) containing mTOR and rictor is thought to be rapamycin insensitive and was recently shown to regulate the prosurvival kinase AKT by phosphorylation on Ser473. We investigated the molecular effects of mTOR inhibition by the rapamycin derivatives (RDs) temsirolimus (CCI-779) and everolimus (RAD001) in acute myeloid leukemia (AML) cells. Unexpectedly,RDs not only inhibited the mTOR complex 1 (mTORC1) containing mTOR and raptor with decreased p70S6K,4EPB1 phosphorylation,and GLUT1 mRNA,but also blocked AKT activation via inhibition of mTORC2 formation. This resulted in suppression of phosphorylation of the direct AKT substrate FKHR and decreased transcription of D-cyclins in AML cells. Similar observations were made in samples from patients with hematologic malignancies who received RDs in clinical studies. Our study provides the first evidence that rapamycin derivatives inhibit AKT signaling in primary AML cells both in vitro and in vivo,and supports the therapeutic potential of mTOR inhibition strategies in leukemias.
The rapamycin-regulated gene expression signature determines prognosis for breast cancer
Molecular Cancer 2009
Abstract
BACKGROUND: Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process or effects of a drug treatment. In this study,we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer. RESULTS: Colony formation and sulforhodamine B (IC50 textless 1 nM) assays,and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature,termed rapamycin metagene index (RMI),of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset,RMI did not correlate with tumor size or lymph node status. High (textgreater75th percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis,RMI (P = 0.029),tumor size (P = 0.015) and lymph node status (P = 0.001) were prognostic. In van 't Veer study,RMI was not associated with the time to develop distant metastasis (P = 0.41). In the Wang dataset,RMI predicted time to disease relapse (P = 0.009). CONCLUSION: Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 53123-88-9 |
| Chemical Formula | C₅₁H₇₉NO₁₃ |
| 纯度 | ≥ 95 % |
| Target | FKBP-12 |
| Pathway | mTOR |
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