Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China.
School of Life Sciences, Jilin University, Changchun, China.
PLoS One. 2019 Nov 8;14(11):e0223738. doi: 10.1371/journal.pone.0223738. eCollection 2019.
The apoptosis-inducing peptide kla (KLAKLAK)2 possesses the ability to disrupt mitochondrial membranes and induce cancer cell apoptosis, but this peptide has a poor eukaryotic cell-penetrating potential. Thus, it requires the assistance of other peptides for effective translocation at micromolar concentrations. In this study, breast and lung cancer cells were treated by kla peptide co-administrated with membrane-active anticancer peptide HPRP-A1. HPRP-A1 assisted kla to enter cancer cells and localized on mitochondrial membranes to result in cytochrome C releasing and mitochondrial depolarization which ultimately induced apoptosis.The apoptosis rate was up to 65%and 45% on MCF-7 and A549 cell lines, respectively, induced by HPRP-A1 coadministration with kla group. The breast cancer model was constructed in mice, and the anticancer peptides were injected to observe the changes in cancer volume, andimmunohistochemical analysis was performed on the tissues and organs after the drug was administered. Both the weight and volume of tumor tissue were remarkable lower in HPRP-A1 with kla group compared with thosepeptidealonggroups. The results showed that the combined drug group effectively inhibited the growth of cancer and did not cause toxic damage to normal tissues, as well as exhibited significantly improvement on peptide anticancer activity in vitro and in vivo.
凋亡诱导肽 kla（KLAKLAK）2 具有破坏线粒体膜并诱导癌细胞凋亡的能力，但该肽对真核细胞的穿透能力较差。因此，它需要其他肽的协助，以在微摩尔浓度下有效转运。在这项研究中，用膜活性抗癌肽 HPRP-A1 与 kla 肽共同处理乳腺癌和肺癌细胞。HPRP-A1 协助 kla 进入癌细胞，并定位于线粒体膜上，导致细胞色素 C 释放和线粒体去极化，最终诱导细胞凋亡。HPRP-A1 与 kla 共同给药组诱导 MCF-7 和 A549 细胞系的凋亡率分别高达 65%和 45%。在小鼠中构建乳腺癌模型，并注射抗癌肽，观察给药后癌症体积的变化，并对组织和器官进行免疫组织化学分析。与单独使用 kla 肽相比，HPRP-A1 联合 kla 组的肿瘤组织重量和体积明显降低。结果表明，联合药物组有效抑制了癌症的生长，对正常组织没有造成毒性损伤，并且显著提高了肽在体外和体内的抗癌活性。
