Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-κB activation through PI3K/Akt pathway.
Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-κB activation through PI3K/Akt pathway.
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汉黄芩苷通过 PI3K/Akt 通路抑制 NF-kappa B 激活，预防炎症相关微环境中结肠炎相关结直肠癌发生和结肠癌进展
DOI：
10.18632/oncotarget.8815
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Lu N
中科院分区：
文献类型：
--
作者：
Sun Y;Zhao Y;Wang X;Zhao L;Li W;Ding Y;Kong L;Guo Q;Lu N
据报道，炎症微环境与肿瘤的发生和恶性发展有关。在以往的研究中，我们发现枸杞皂苷具有抗肿瘤和抗炎活性。在本研究中，我们旨在进一步研究枸杞皂苷对结肠炎相关癌症的化学预防作用，并描述其可能的机制。在偶氮甲烷引发和葡聚糖硫酸钠（AOM/DSS）促进结直肠癌发生的小鼠模型中，枸杞皂苷显著降低疾病严重程度，降低肿瘤发生率，抑制结直肠腺瘤的发展。枸杞皂苷对肿瘤部位的炎性细胞浸润和癌细胞增殖有抑制作用。此外，枸杞子皂苷显著降低了腺瘤及周围组织中IL-1β、IL-6、TNF-α的分泌和表达以及NF-κB的核表达。体外实验结果表明，枸杞皂苷能抑制人结肠癌细胞在炎症微环境中的增殖。在机制上，我们发现枸杞皂苷通过PI3K/Akt途径抑制NF-κB的激活。综上所述，我们的研究结果表明，枸杞皂苷通过抑制PI3K/Akt通路中NF-κB的激活，减轻了小鼠结肠炎相关肿瘤的发生，抑制了炎症相关微环境中人类结肠癌的进展，表明枸杞皂苷可能是一种有前景的结直肠癌治疗药物。
The inflammatory microenvironment has been reported to be correlated with tumor initiation and malignant development. In the previous studies we have found that wogonoside exerts anti-neoplastic and anti-inflammatory activities. In this study, we aimed to further investigate the chemopreventive effects of wogonoside on colitis-associated cancer and delineated the potential mechanisms. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, wogonoside significantly reduced the disease severity, lowered tumor incidence and inhibited the development of colorectal adenomas. Moreover, wogonoside inhibited inflammatory cells infiltration and cancer cell proliferation at tumor site. Furthermore, wogonoside dramatically decreased the secretion and expression of IL-1β, IL-6 and TNF-α as well as the nuclear expression of NF-κB in adenomas and surrounding tissues. In vitro results showed that wogonoside suppressed the proliferation of human colon cancer cells in the inflammatory microenvironment. Mechanistically, we found that wogonoside inhibited NF-κB activation via PI3K/Akt pathway. In conclusion, our results demonstrated that wogonoside attenuated colitis-associated tumorigenesis in mice and inhibited the progression of human colon cancer in inflammation-related microenvironment via suppressing NF-κB activation by PI3K/Akt pathway, indicating that wogonoside could be a promising therapeutic agent for colorectal cancer.
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影响因子：
3.5
作者：
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DOI：
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