Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers.

Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers.
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DOI:
10.1371/journal.pone.0042685
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Ma D
Ma D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ma X;Xi L;Luo D;Liu R;Li S;Liu Y;Fan L;Ye S;Yang W;Yang S;Meng L;Zhou J;Wang S;Ma D

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癌症如寡核苷酸或肽的治疗需要有效的递送系统。一种新的肽,TMTP 1,以前在我们的实验室中衍生和鉴定显示出显着的能力,靶向高转移性肿瘤在体外和体内,即使在早期阶段的隐匿性转移灶。TMTP 1适度抑制肿瘤细胞活力,尽管不足以认为它是肿瘤细胞的有效杀伤者。在这项研究中,我们试图增强TMTP 1的抗肿瘤活性。为此,我们将其与抗菌肽D(KLAKLAK)2融合,并将所得肽称为TMTP 1-DKK。我们发现TMTP 1-DKK可以通过细胞诱导凋亡途径和死亡受体途径引发人前列腺癌和胃癌细胞的快速凋亡。此外,将TMTP 1-DKK直接注射到患有前列腺和胃异种移植癌的小鼠中导致肿瘤体积的减小和体内肿瘤进展和转移的显著延迟。这些结果表明,TMTP 1-DKK可能作为一个强大的治疗剂转移性肿瘤。
The treatment of cancer such as oligonucleotides or peptides requires efficient delivery systems. A novel peptide, TMTP1, previously derived and identified in our laboratory showed remarkable ability to target highly metastatic tumors both in vitro and in vivo, even at the early stage of occult metastasis foci. TMTP1 moderately inhibited tumor cell viability, although not enough to deem it an efficient killer of tumor cells. In this study, we sought to enhance the anti-tumor activity of TMTP1. To do this, we fused it to an antimicrobial peptide, D(KLAKLAK)2, and termed the resulting peptide TMTP1-DKK. We found that TMTP1-DKK could trigger rapid apoptosis in human prostate and gastric cancer cells through both the mitochondrial-induced apoptosis pathway and the death receptor pathway. Furthermore, direct injection of TMTP1-DKK into mice with prostate and gastric xenograft cancers resulted in reduction of tumor volumes and a significant delay in tumor progression and metastasis in vivo. These results suggest that TMTP1-DKK may serve as a powerful therapeutic agent for metastatic tumors.
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