Traditional Chinese Medicine Department, Changzhou First People's Hospital, 185th on Juqian street, Changzhou, 213000, China.
Department of Oncology, Changzhou First People's Hospital, 185th on Juqian street, Changzhou, 213000, China.
Biomed Pharmacother. 2018 Sep;105:758-765. doi: 10.1016/j.biopha.2018.06.028. Epub 2018 Jun 14.
This study aims to explore the effects and related mechanisms of Tanshinone IIA in cervix carcinoma (CC) stemness-like cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that Tanshinone IIA suppressed CC stemness-like cells migration and invasion in a concentration- and time-dependent manner. And consistent results were obtained in CC cells stemness characterized as the decrease of CC stemness markers expression and cells spheroid formation ability. Mechanistically, we found that Tanshinone IIA suppressed RNA binding protein HuR translocation from nuclear to cytoplasm, and thus reduced YAP mRNAs stability and transcriptional activity. Importantly, overexpression YAP-5SA rescued the inhibition of Tanshinone IIA on CC cells stemness. Furthermore, Tanshinone IIA enhanced adriamycin sensitivity in CC stemness-like cells, this effect was attenuated by YAP-5SA overexpression too. Therefore, Tanshinone IIA could suppress CC stemness-like cells migration and invasion by inhibiting YAP transcriptional activity.
本研究旨在探讨丹参酮 IIA 对宫颈癌（CC）干细胞样细胞迁移、侵袭、干性和化疗敏感性的影响及相关机制。研究发现，丹参酮 IIA 呈浓度和时间依赖性地抑制 CC 干细胞样细胞的迁移和侵袭。并且在 CC 细胞干性特征中也得到了一致的结果，表现为 CC 干性标志物表达降低和细胞球体形成能力下降。在机制上，研究发现丹参酮 IIA 抑制 RNA 结合蛋白 HuR 从核内易位到细胞质，从而降低 YAP mRNAs 的稳定性和转录活性。重要的是，过表达 YAP-5SA 可挽救丹参酮 IIA 对 CC 细胞干性的抑制作用。此外，丹参酮 IIA 增强了 CC 干细胞样细胞对阿霉素的敏感性，而过表达 YAP-5SA 也减弱了这种作用。因此，丹参酮 IIA 可以通过抑制 YAP 转录活性来抑制 CC 干细胞样细胞的迁移和侵袭。
