Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan.
Peptides. 2010 Jun;31(6):1019-25. doi: 10.1016/j.peptides.2010.02.023. Epub 2010 Mar 7.
The antitumor activity of the shrimp anti-lipopolysaccharide factor (SALF), an antimicrobial peptide, was not previously examined. In this study, a synthetic SALF was tested for antitumor activity using HeLa cells as the study model. We show that the SALF inhibited the proliferation of HeLa cells and reduced colony formation in a soft agar assay. An enhanced effect was observed when the SALF and cisplatin were used in combination, which caused significant inhibition of HeLa cells. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the SALF altered the membrane structure similar to what a lytic peptide does. A flow cytometric analysis, qRT-PCR, and Western blotting showed that the SALF induced apoptosis, activated caspases-6, -7, and -9, and downregulated Bcl-2 and nuclear factor (NF)-kappaB suggesting that the SALF induces apoptosis through the death receptor/NF-kappaB signaling pathway. An in vivo analysis revealed that the SALF displayed significant tumor suppressive activity in mice with tumor xenografts. Overall, these results indicated that the SALF possesses the potential to be a novel therapeutic agent for treating cervical cancer.
虾抗脂多糖因子（SALF）是一种抗菌肽，其抗肿瘤活性此前尚未被研究过。在本研究中，以 HeLa 细胞为研究模型，检测了合成的 SALF 的抗肿瘤活性。结果表明，SALF 抑制了 HeLa 细胞的增殖，并减少了软琼脂实验中的集落形成。当 SALF 和顺铂联合使用时，观察到增强的效果，这导致 HeLa 细胞的显著抑制。扫描电子显微镜（SEM）和透射电子显微镜（TEM）显示，SALF 改变了膜结构，类似于溶细胞肽的作用。流式细胞术分析、qRT-PCR 和 Western blot 显示，SALF 诱导了细胞凋亡，激活了半胱天冬酶-6、-7 和 -9，并下调了 Bcl-2 和核因子（NF）-kappaB，表明 SALF 通过死亡受体/NF-kappaB 信号通路诱导细胞凋亡。体内分析表明，SALF 在携带肿瘤异种移植物的小鼠中表现出显著的肿瘤抑制活性。总的来说，这些结果表明 SALF 具有成为治疗宫颈癌的新型治疗剂的潜力。
