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Brit J Cancer:Nintedanib:肝内胆管癌的新福音——尼达尼布!

2020-02-10 不详 MedSci原创

肝内胆管癌(ICC)是一种极难治愈的恶性肿瘤。ICC组织中的成纤维细胞已被鉴定为可以促进ICC细胞恶性行为反应的癌症相关成纤维细胞(CAF)。据报道,抗纤维化药物尼达尼布(nintedanib)作为多种酪氨酸激酶的小分子抑制剂,可抑制肝星状细胞的激活。本研究旨在阐明尼达尼布是否可以抑制ICC组织来源的CAF的促癌作用。研究人员发现CAFs可以促进ICC细胞的增殖及侵袭。α-平滑肌肌动蛋白(α-SM

肝内胆管癌(ICC)是一种极难治愈的恶性肿瘤。ICC组织中的成纤维细胞已被鉴定为可以促进ICC细胞恶性行为反应的癌症相关成纤维细胞(CAF)。据报道,抗纤维化药物尼达尼布(nintedanib)作为多种酪氨酸激酶的小分子抑制剂,可抑制肝星状细胞的激活。

本研究旨在阐明尼达尼布是否可以抑制ICC组织来源的CAF的促癌作用。

研究人员发现CAFs可以促进ICC细胞的增殖及侵袭。α-平滑肌肌动蛋白(α-SMA)可以作为活化CAFs的一种标志物,而尼达尼布可以抑制活化的CAF表达α-SMA,并抑制CAF对ICC的促癌作用。尼达尼布可以显著减少CAF分泌的促癌细胞因子,如白介素IL-6和IL-8。体内研究表明,尼达尼布能够降低ICC移植瘤的生长并激活CAF表达α-SMA。相较于对照组及单药物治疗组,尼达尼布与吉西他滨(gemcitabine)联合治疗对CAF及ICC的生长抑制效果最佳,该联合治疗可以显著减小移植瘤模型中的肿瘤体积。

综上所述,尼达尼布可以通过抑制CAF的活化及促癌细胞因子的分泌进而抑制CAF的促癌作用。该研究结果表明,常规细胞毒性药物(如吉西他滨)及靶向CAF的药物尼达尼布的联合治疗策略有望攻克肝内胆管癌这一难治的的恶性肿瘤。

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