Study of antitumor effect and dendritic cells induced by human Cathelicidin hCAP18.

HCAP18，一个单独的人源阳离子抗菌蛋白，属于长春新素家族。我们先前的研究结果显示，Hcap18可导致口腔鳞状细胞癌(OSCC)细胞线粒体膜电位的丧失和死亡，但不会导致健康人角质形成细胞和牙龈成纤维细胞的死亡。在这里，我们论证了hCAP18肽诱导的口腔鳞状细胞癌细胞凋亡是否以caspase非依赖的方式介导。我们的研究发现，hCAP18通过促凋亡蛋白Bax控制的线粒体途径诱导细胞凋亡。Bax持续诱导Endo G从线粒体释放到胞浆和胞核。此外，我们还研究了hCAP18对口腔鳞状细胞癌体内生长的影响，我们用hCAP18多肽每天一次注射治疗移植了SAS-H1/GFP细胞的裸鼠。在hCAP18治疗2天后，肿瘤生长明显受到抑制，与扰乱多肽治疗的对照组相比。经hCAP18处理的小鼠口腔鳞状细胞癌移植瘤明显减少。这些结果表明，hCAP18触发了caspase非依赖的凋亡通路，从而提供了人口腔鳞癌的抗肿瘤作用。此外，hCAP18肽促进树突状细胞分化，连接先天免疫和获得性免疫反应。

The hCAP18, a solo human cationic antimicrobial protein of cathelicidin family. Our previously results that hCAP 18 induced loss of mitochondrial membrane potential and death in human oral squamous cell carcinoma (OSCC) cells, but not healthy human keratinocytes and gingival fibroblast cells. Here, we demonstrate that whether hCAP18 peptide-induced apoptosis could mediate a caspase-independent manner in OSCC cells. Our finding that hCAP18-induced apoptosis through a mitochondrial pathway of apoptosis controlled by proapoptotic protein Bax. Continuously, Bax induced the release of Endo G from the mitochondria to cytosol and nucleus, respectively. Furthermore, we investigate the effects of hCAP18 on OSCC growth in vivo, we treated nude mice carrying SAS-H1/GFP cells xenograftings with once-daily injections of hCAP18 peptide. Tumor growth was significantly inhibited after 2 days of hCAP18 treatment, compared to scramble peptide-treated controls. OSCC xenografts tumors from mice treated with hCAP18 displayed predominantly reduction. These results suggest that hCAP18 triggered caspase-independent apoptotic pathway, thereby providing antitumor effect of human OSCC. In addition, hCAP18 peptide promotes dendritic cell differentiation, bridging innate and adaptive immune responses.