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用 WNT 抑制剂和双功能肽联合靶向治疗肾癌。

Targeting renal cancer with a combination of WNT inhibitors and a bi-functional peptide.

机构信息

Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, 53105 Bonn, Germany.

出版信息

Anticancer Res. 2013 Jun;33(6):2435-40.

Abstract

AIM

Advanced renal cancer has still a very poor prognosis. We combined wingless-related integration site (WNT) inhibitors with a bi-functional peptide, as previous research has proven their individual efficacy in cancer therapy. Each targets cancer cells differently. We wanted to determine whether they have an additive effect.

MATERIALS AND METHODS

Our bi-functional peptide consists of a target domain (LTVSPWY) and a lytic domain (KLAKLAK)2. We used three WNT inhibitors: Ethacrinic acid, ciclopirox olamine, piroctone olamine and combined each with the bi-functional peptide. They were tested on three different renal cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay.

RESULTS

We demonstrated a synergistic effect of WNT inhibitors with the bi-functional peptide. The vitality of cancer cells was reduced significantly (p<0.05), while healthy cells were mostly unaffected.

CONCLUSION

The combination of WNT inhibitor and the bi-functional peptide may lead to new treatment options as toxic side-effects can be reduced due to the lower doses of agent required.

摘要

目的

晚期肾癌预后仍然很差。我们将 Wnt 相关整合位点(WNT)抑制剂与双功能肽结合,因为之前的研究已经证明它们在癌症治疗中的单独疗效。它们的作用靶点不同。我们想确定它们是否具有相加作用。

材料和方法

我们的双功能肽由一个靶结构域(LTVSPWY)和一个裂解结构域(KLAKLAK)2 组成。我们使用了三种 WNT 抑制剂:Ethacrinic acid、环吡罗司胺、吡咯酮乙醇胺,并将每种抑制剂与双功能肽结合。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法在三种不同的肾癌细胞系上测试了它们。

结果

我们证明了 WNT 抑制剂与双功能肽的协同作用。癌细胞活力明显降低(p<0.05),而健康细胞大多不受影响。

结论

Wnt 抑制剂与双功能肽的联合使用可能会带来新的治疗选择,因为所需药物剂量较低,毒性副作用可能会降低。

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