Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, 53105 Bonn, Germany.
Anticancer Res. 2013 Jun;33(6):2435-40.
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.
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.
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.
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.
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。
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。
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。
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。