Tianjin Central Hospital of Gynecology Obstetrics, No. 156 Nankai San Ma Road, Nankai District, Tianjin, 300100, China; Research Institute of Obstetrics and Gynecology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, China.
Clinical School of Obstetrics and Gynecology Center, Tianjin Medical University, No. 22 Meteorological Observatory Road, Heping District, Tianjin, 300070, China; Tianjin Medical University, No. 22 Meteorological Observatory Road, Heping District, Tianjin, 300070, China.
Arch Biochem Biophys. 2023 Jul 15;743:109655. doi: 10.1016/j.abb.2023.109655. Epub 2023 Jun 5.
Endometrial carcinoma is the most common gynecological tumor in developed countries. Tanshinone IIA is a traditional herbal medicine which is to treat cardiovascular disease and has been shown to have various biological effects, such as anti-inflammatory, antioxidative and antitumor activities. However, there has been no study about the effect of tanshinone IIA on endometrial carcinoma. Thus, the aim of this study was to determine the antitumor activity of tanshinone IIA against endometrial carcinoma and investigate the associated molecular mechanism. We demonstrated that tanshinone IIA induced cell apoptosis and inhibited migration. We further demonstrated that tanshinone IIA activated the intrinsic (mitochondrial) apoptotic pathway. Mechanistically, tanshinone IIA induced apoptosis by upregulating TRIB3 expression and inhibiting the MAPK/ERK signaling pathway. In addition, knockdown of TRIB3 with an shRNA lentivirus accelerated proliferation and attenuated inhibition mediated by tanshinone IIA. Finally, we further demonstrated that tanshinone IIA inhibited tumor growth by inducing TRIB3 expression in vivo. In conclusion, these findings suggest that tanshinone IIA has a significant antitumor effect by inducing apoptosis and may be used as a drug for the treatment of endometrial carcinoma.
子宫内膜癌是发达国家最常见的妇科肿瘤。丹参酮 IIA 是一种传统的草药，用于治疗心血管疾病，已显示出具有多种生物学效应，如抗炎、抗氧化和抗肿瘤活性。然而，目前还没有关于丹参酮 IIA 对子宫内膜癌影响的研究。因此，本研究旨在确定丹参酮 IIA 对子宫内膜癌的抗肿瘤活性，并探讨相关的分子机制。我们证明丹参酮 IIA 诱导细胞凋亡并抑制迁移。我们进一步证明丹参酮 IIA 激活了内在（线粒体）凋亡途径。在机制上，丹参酮 IIA 通过上调 TRIB3 表达和抑制 MAPK/ERK 信号通路诱导细胞凋亡。此外，用 shRNA 慢病毒敲低 TRIB3 可加速增殖并减弱丹参酮 IIA 介导的抑制作用。最后，我们进一步证明丹参酮 IIA 通过诱导体内 TRIB3 表达来抑制肿瘤生长。总之，这些发现表明丹参酮 IIA 通过诱导细胞凋亡具有显著的抗肿瘤作用，可能可用于治疗子宫内膜癌的药物。
