黄芩苷通过 TLR4/NF-κB 信号通路在结直肠癌中触发凋亡、抑制迁移并增强抗肿瘤免疫,Journal of Food Biochemistry

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黄芩苷通过 TLR4/NF-κB 信号通路在结直肠癌中触发凋亡、抑制迁移并增强抗肿瘤免疫
Journal of Food Biochemistry ( IF 3.5 ) Pub Date : 2021-03-20 , DOI: 10.1111/jfbc.13703
Linjiang Song ₁ , Shaomi Zhu ₁ , Chi Liu ₁ , Qinxiu Zhang ₁ , Xin Liang ₁

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核因子-κB (NF-κB) 信号通路的异常激活与结直肠癌 (CRC) 的生长、转移和免疫逃逸密切相关。在本研究中，我们报道了黄芩苷（BA）的天然衍生化合物，一种有效的NF-κB抑制剂，对CRC具有良好的抗肿瘤作用。CCK8 和集落形成测定表明，黄芩苷显着抑制 HCT-116 和 CT26 细胞的活力和增殖。此外，黄芩苷可显着触发 HCT-116 和 CT-26 细胞中线粒体介导的细胞凋亡，这可以通过线粒体膜电位的丧失和细胞活性氧水平升高来证明。黄芩苷处理通过损害 TLR4/NF-κB 信号通路来抑制 CT26 细胞的迁移和侵袭。更重要的是，在 CT26 细胞的皮下异种移植肿瘤小鼠模型中，黄芩苷的给药显着延缓了肿瘤生长速率。黄芩苷治疗可通过下调 PD-L1 表达和髓源性抑制细胞 (MDSC) 比例以及上调 CD4 百分比来改善肿瘤免疫抑制环境^{CT26 肿瘤中的+}和 CD8 ⁺ T 细胞，从而提高抗肿瘤免疫力。总之，我们的研究表明，黄芩苷通过 TLR4/NF-κB 信号通路在结直肠癌中触发细胞凋亡、抑制迁移和增强抗肿瘤免疫，表明它可能作为治疗 CRC 的潜在候选药物。

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Baicalin triggers apoptosis, inhibits migration, and enhances anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway

Aberrant activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in colorectal cancer (CRC) growth, metastasis, and immune escape. In the present study, we reported natural derived compound of baicalin (BA), an efficient inhibitor of NF-κB, with good anti-tumor effect on CRC. CCK8 and colony formation assays showed that Baicalin significantly inhibit viability and proliferation in HCT-116 and CT26 cells. Additionally, Baicalin dramatically triggers mitochondria-mediated apoptosis in both HCT-116 and CT-26 cells, which is evidenced by loss of mitochondrial membrane potential and elevated cellular reactive oxygen species level. Treatment with Baicalin suppresses migration and invasion of CT26 cells by impairing TLR4/NF-κB signaling pathway. What's more, administration of Baicalin significantly retarded tumor growth rate in a subcutaneous xenograft tumor mouse model of CT26 cells. Treatment with Baicalin could ameliorate tumor immunosuppressive environment by downregulation of PD-L1 expression and proportion of myeloid-derived suppressor cells (MDSCs) and upregulation of percent of CD4⁺ and CD8⁺ T cells in CT26 tumors, thus improving anti-tumor immunity. In conclusion, our study demonstrated that baicalin triggers apoptosis, inhibits migration, and enhances anti-tumor immunity in colorectal cancer via TLR4/NF-κB signaling pathway, suggesting it might serve as a potential candidate drug for the treatment of CRC.

更新日期：2021-03-20

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