CecropinXJ inhibits the proliferation of human gastric cancer BGC823 cells and induces cell death in vitro and in vivo
CecropinXJ inhibits the proliferation of human gastric cancer BGC823 cells and induces cell death in vitro and in vivo
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DOI：
10.3892/ijo.2015.2933
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发表时间：
2015-05-01
影响因子：
5.2
通讯作者：
Zhang, Fu-Chun
中科院分区：
文献类型：
--
作者：
Wu, Yan-Ling;Xia, Li-Jie;Zhang, Fu-Chun
我们已经证明，抗菌肽（AMP）cecropinXJ分离自家蚕幼虫选择性抑制癌细胞的增殖。然而，其机制仍有待确定。本实验研究了抗菌肽XJ对人胃癌BGC 823细胞的抗肿瘤作用，并探讨了其作用机制。结果表明，抗菌肽XJ在体内外均能抑制胃癌BGC 823细胞的生长。MTT法和集落形成实验表明，抗菌肽XJ能抑制胃癌BGC 823细胞的增殖和集落形成，且呈剂量和时间依赖性，但对正常胃上皮GES-1细胞无抑制作用。CecropinXJ作用于BGC 823细胞后，细胞周期出现S期阻滞。Annexin V/PI染色结果显示，抗菌肽XJ通过激活caspase通路，上调Bax表达，下调Bcl-1 -2表达，诱导细胞凋亡的早期和晚期。此外，天蚕抗菌肽处理增加了活性氧（ROS）的产生，破坏了线粒体膜电位（6apin），并导致细胞色素c的释放。重要的是，体内研究表明，cecropinXJ显着防止BGC 823荷瘤小鼠的异种移植瘤的生长，可能通过诱导细胞凋亡和抑制血管生成介导。这些结果表明，抗菌肽XJ可能是一个有前途的治疗胃癌的候选药物。
We have shown that an antimicrobial peptide (AMP) cecropinXJ isolated from the larvae of Bombyx mori selectively inhibits the proliferation of cancer cells. However, the mechanism remains to be determined. In the present study, we examined the antitumor activity of cecropinXJ against human gastric cancer BGC823 cells and explored the mechanism. The results showed that cecropinXJ inhibited the growth of gastric cancer BGC823 cells in vitro and in vivo. MTT and colony formation assays indicated that cecropinXJ suppressed cell proliferation and reduced colony formation of BGC823 cells in a dose- and time-dependent manner, but without inhibitory effect on normal gastric epithelia GES-1 cells. S-phase arrest in BGC823 cells was observed after treatment with cecropinXJ. Annexin V/PI staining suggested that cecropinXJ induced both early and late phases of apoptosis through activation of mitochondrial-mediated caspase pathway, upregulation of Bax expression and downregulation of Bc1-2 expression. Additionally, cecropinXJ treatment increased reactive oxygen species (ROS) production, disrupted the mitochondrial membrane potential (6apin) and led to release of cytochrome c. Importantly, in vivo study showed that cecropinXJ significantly prevented the growth of xenograft tumor in the BGC823-bearing mice, possibly mediated by the induction of apoptosis and inhibition of angiogenesis. These results suggest that cecropinXJ may be a promising therapeutic candidate for the treatment of gastric cancer.