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Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells

上皮-间质转换 转移 结直肠癌 癌症研究 CpG站点 癌症 医学 癌细胞 波形蛋白 病理 化学 内科学 DNA甲基化 免疫组织化学 基因表达 基因 生物化学
作者
Hong‐Yong Jin,Sujie Gao,Defeng Song,Yiting Liu,Xuebo Chen
出处
期刊:Anti-Cancer Drugs [Ovid Technologies (Wolters Kluwer)]
卷期号:32 (3): 278-285 被引量:15
标识
DOI:10.1097/cad.0000000000001000
摘要

Colon cancer liver metastasis accounts for the major cause of death of colon cancer patients. Previous study reported a carbon nanotubes (CNT)-conjugated CpG complex (CNT-CpG), which displayed a significant antitumor effect in gliomas. However, whether CNT-CpG could limit colon tumor growth and suppress the colon cancer liver metastasis has not been evaluated. In this study, we report CNT enhances CpG uptake in mouse colon cancer cells. Results demonstrated only CpG with CNT conjugation showed significant activation of NF-κB signal. Moreover, intratumorally delivery of CNT-CpG successfully suppressed local xenograft tumor growth and liver metastasis. CNT-CpG treatments cured 75% of mice and inhibited local tumor growth, significantly prolonged survival outcomes and limited liver metastatic tumor nodules from colon cancer cells. Using human colon cancer cell line, HCT116, we observed significantly inhibitory effects of CNT-CpG on cell growth, invasion and migration. Importantly, CNT-CpG treatment blocked the epithelial to mesenchymal transition (EMT). We compared the mRNA levels of EMT markers of colon cancer cells without or with CNT-CpG treatment from in-vitro and in-vivo models. Consistent results demonstrated expression of epithelial marker, E-cadherin was upregulated by CNT-CpG. In contrast, three mesenchymal markers, snail, fibronectin and vimentin were significantly suppressed by CNT-CpG treatment compared with control or free CpG. In summary, our data suggest CNT-CpG is an effective therapeutic approach against local colon tumor and their liver metastasis. This study presents the CNT-CpG complex as a promising therapeutic target for developing novel therapies against both local colon tumors and liver metastatic tumors.
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