Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University Changsha Hunan 410005, P. R. China.
Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University Changsha Hunan 410005, P. R. China.
Am J Chin Med. 2023;51(3):701-721. doi: 10.1142/S0192415X23500337. Epub 2023 Feb 23.
Intrahepatic cholangiocarcinoma (ICC) is a rare, highly fatal hepatobiliary malignancy, with very limited treatment options and, consequently, a poor prognosis. Recently, emerging evidence has suggested the potential of quercetin (QE) for use in cancer therapy. The purpose of this study is to investigate whether QE could inhibit ICC. The effects of QE on the proliferation, apoptosis, and invasion of ICC were analyzed . The inhibitory effect of QE on ICC was also verified . The RNA sequence was applied to explore the mechanism of QE. Functional verification was also performed after RNA sequencing using activators and inhibitors of nuclear factor-kappa-B (NF-[Formula: see text]B) and ferroptosis. The results showed that QE could inhibit the proliferation and survival of ICC cells, induce the arrest of ICC cells in the G1 phase, promote the apoptosis of ICC cells, and inhibit the invasion of ICC cells. Furthermore, QE could promote ferroptosis in ICC cells by inhibiting the NF-[Formula: see text]B pathway. In conclusion, QE is a new ferroptosis inducer and NF-[Formula: see text]B inhibitor that can not only induce ferroptosis, but also inhibit the invasion of ICC cells, providing a prospective strategy for the treatment of ICC.
肝内胆管癌（ICC）是一种罕见的、致命的肝胆恶性肿瘤，治疗选择非常有限，因此预后较差。最近，新出现的证据表明槲皮素（QE）在癌症治疗中的应用潜力。本研究旨在探讨 QE 是否能抑制 ICC。分析了 QE 对 ICC 增殖、凋亡和侵袭的影响。验证了 QE 对 ICC 的抑制作用。应用 RNA 测序探讨 QE 的作用机制。RNA 测序后还使用核因子-κB（NF-κB）和铁死亡的激活剂和抑制剂进行了功能验证。结果表明，QE 能抑制 ICC 细胞的增殖和存活，诱导 ICC 细胞 G1 期阻滞，促进 ICC 细胞凋亡，抑制 ICC 细胞侵袭。此外，QE 通过抑制 NF-κB 通路促进 ICC 细胞铁死亡。总之，QE 是一种新的铁死亡诱导剂和 NF-κB 抑制剂，不仅能诱导铁死亡，还能抑制 ICC 细胞的侵袭，为 ICC 的治疗提供了一种有前景的策略。
