Curcumin may be a potential adjuvant treatment drug for colon cancer by targeting CD44

Curcumin may be a potential adjuvant treatment drug for colon cancer by targeting CD44
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姜黄素可能是靶向CD44的潜在结肠癌辅助治疗药物

DOI:
10.1016/j.intimp.2020.106991
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发表时间:
2020-11-01
影响因子:
5.6
通讯作者:
Du, Boyu
Du, Boyu
中科院分区:
医学2区
文献类型:
--
作者:
Fan, Xu;Zhu, Min;Du, Boyu

文献摘要

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尽管治疗方法的发展取得了长足的进步,但结肠癌相关的死亡率仍位居所有肿瘤相关疾病的第五位。近年来,越来越多的证据支持结肠癌干细胞的存在可能是结肠癌发生、发展和复发的主要原因之一。姜黄素已被证明具有抗癌活性。也有研究表明,姜黄素通过与CD44结合而发挥抗结直肠癌的作用。CD44是结直肠癌的重要标志物和重要功能分子。在本研究中,我们证实了姜黄素可以抑制结肠癌细胞的增殖、集落形成、迁移和肿瘤球体的形成。实时定量聚合酶链式反应和免疫印迹结果表明,姜黄素可以下调CD44的表达。此外,流式细胞术的结果进一步表明,姜黄素可以降低CD44(+)结肠癌细胞的比例。用siRNA下调CD44的表达后,姜黄素对CD44(+)结肠癌细胞的抑制作用明显减弱。此外,还观察到CD44(+)结肠癌细胞对姜黄素的摄取显著增加。流式细胞仪检测结果显示,姜黄素可诱导CD44(+)结肠癌细胞发生凋亡。综上所述,我们的结果提示姜黄素可能通过靶向CD44而成为治疗结直肠癌的辅助药物。
Despite the considerable advances in treatment method development, the mortality rate related to colon cancer still ranks the fifth in all tumor-related diseases. Recently, there has been growing evidences supporting the existence of colon cancer stem cells (CSCs) might be one of the main causes for initiation, progression and recurrence of colon cancer. Curcumin has been shown to possess anticancer activities. It has also been suggested that curcumin was effective against colon CSCs by coupling with CD44, a robust marker and functional important molecule for colorectal CSC. In the present study, we confirmed that curcumin can inhibit the proliferation, colony formation, migration and tumor sphere formation of colon cancer cells. Results from real-time PCR and western blotting had suggested that curcumin could down-regulate the expression of CD44. Moreover, results from flow cytometry had further revealed that curcumin could decrease the proportion of CD44(+) colon cancer cells. After the expression of CD44 had been knocked down by using siRNA, the inhibition effects of curcumin against CD44(+) colon cancer cells were observed to be reduced significantly. Moreover, it had been observed that the cellular uptake of curcumin was significantly higher in CD44(+) colon cancer cells. Results from flow cytometry had shown that curcumin could induce apoptosis in CD44(+) colon cancer cells. Altogether, our results suggested that curcumin might be an adjuvant drug for the treatment of colorectal cancer by targeting CD44.