Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
PLoS One. 2012;7(9):e42685. doi: 10.1371/journal.pone.0042685. Epub 2012 Sep 11.
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.
癌症的治疗，如寡核苷酸或肽，需要高效的递送系统。一种新型的肽，TMTP1，是我们实验室之前衍生和鉴定的，它表现出显著的靶向高转移性肿瘤的能力，无论是在体外还是体内，甚至在隐匿性转移灶的早期阶段。TMTP1 适度抑制肿瘤细胞的活力，尽管不足以将其视为肿瘤细胞的有效杀伤剂。在这项研究中，我们试图增强 TMTP1 的抗肿瘤活性。为此，我们将其与一种抗菌肽（D）（KLAKLAK）（2）融合，将得到的肽命名为 TMTP1-DKK。我们发现 TMTP1-DKK 可以通过线粒体诱导的凋亡途径和死亡受体途径触发人前列腺癌和胃癌细胞的快速凋亡。此外，将 TMTP1-DKK 直接注射到患有前列腺癌和胃癌异种移植癌的小鼠体内，可导致肿瘤体积缩小，并显著延缓体内肿瘤的进展和转移。这些结果表明，TMTP1-DKK 可能成为转移性肿瘤的一种强大的治疗剂。
