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莪术醇通过下调CDKL3对胆管癌细胞发挥抗癌作用。

Curcumol Exerts Anticancer Effect in Cholangiocarcinoma Cells via Down-Regulating CDKL3.

作者信息

Zhang Jinduo, Su Gang, Tang Zengwei, Wang Li, Fu Wenkang, Zhao Sheng, Ba Yongjiang, Bai Bing, Yue Ping, Lin Yanyan, Bai Zhongtian, Hu Jinjing, Meng Wenbo, Qiao Liang, Li Xun, Xie Xiaodong

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Front Physiol. 2018 Mar 20;9:234. doi: 10.3389/fphys.2018.00234. eCollection 2018.

Abstract

Curcumol is the major component extracted from root of . Recent studies have shown that curcumol exerts therapeutic effects against multiple conditions, particularly cancers. However, the therapeutic role and mechanism of curcumol against cholangiocarcinoma cells are still unclear. In our current research, we tested the effect of curcumol in cholangiocarcinoma cells, and using two-dimensional electrophoresis, proteomics and bioinformatics, we identified cyclin-dependent kinase like 3 (CDKL3) as a potential target for curcumol. We have demonstrated that curcumol can evidently suppress growth and migration of cholangiocarcinoma cells. Furthermore, curcumol could significantly block the cell cycle progression of the cholangiocarcinoma cells. These effects could be largely attributed to the inhibition of CDKL3 by curcumol. Further studies have recapitulated the oncogenic role of CDKL3 in that knockdown of CDKL3 by lentiviral mediated transfection of shRNA against CDKL3 also led to a significant inhibition on cell proliferation, migration, invasion, and cell cycle progression. Given the high level of CDKL3 expression in human cholangiocarcinoma tissues and cell lines, we speculated that CDKL3 may constitute a potential biological target for curcumol in cholangiocarcinoma.

摘要

莪术醇是从[植物名称]根中提取的主要成分。最近的研究表明,莪术醇对多种病症具有治疗作用,尤其是癌症。然而,莪术醇对胆管癌细胞的治疗作用和机制仍不清楚。在我们当前的研究中,我们测试了莪术醇对胆管癌细胞的作用,并使用二维电泳、蛋白质组学和生物信息学,我们鉴定出细胞周期蛋白依赖性激酶样3(CDKL3)是莪术醇的一个潜在靶点。我们已经证明,莪术醇可以明显抑制胆管癌细胞的生长和迁移。此外,莪术醇可以显著阻断胆管癌细胞的细胞周期进程。这些作用很大程度上可归因于莪术醇对CDKL3的抑制。进一步的研究重现了CDKL3的致癌作用,即通过慢病毒介导的针对CDKL3的短发夹RNA(shRNA)转染敲低CDKL3也导致对细胞增殖、迁移、侵袭和细胞周期进程的显著抑制。鉴于CDKL3在人胆管癌组织和细胞系中高表达,我们推测CDKL3可能构成莪术醇在胆管癌中的一个潜在生物学靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac87/5870041/18c2ccd209da/fphys-09-00234-g0001.jpg

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