Department of Gynecology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurosurgery, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
J Pharm Pharmacol. 2018 Oct;70(10):1369-1377. doi: 10.1111/jphp.12961. Epub 2018 Jun 25.
To explore the potential therapeutic effect of Tanshinone IIA against ovarian cancer in vitro and elucidate the underlying molecular mechanism.
The cell survival upon Tanshinone IIA treatment was determined by the clonogenic assay. Cell apoptosis was analysed by Annexin V/propidium iodide double staining. The cleaved caspase-3/poly ADP-ribose polymerase and apoptosis-related factors were quantified by Western blotting. The relative expression of microRNAs (miRs) was determined by real-time polymerase chain reaction.
Tanshinone IIA treatment induced significant apoptosis in TOV-21G cells. Tanshinone suppressed survivin expression while not affected Bax, Bcl-2 and Bcl-xL. We further predicted and experimentally confirmed overexpression of miR-205 in TOV-21G, which ectopic significantly inhibited survivin and promoted cell apoptosis. miR-205-specific antagonist completely abrogated the cell suppressive effect of Tanshinone IIA.
Our data suggested that Tanshinone IIA induced cell apoptosis in ovarian carcinoma TOV-21G cells via direct upregulation of miR-205. Our study highlighted the potential therapeutic application of Tanshinone IIA against ovarian malignancy.
探讨丹参酮 IIA 对体外卵巢癌的潜在治疗作用，并阐明其潜在的分子机制。
通过集落形成实验测定丹参酮 IIA 处理后的细胞存活率。通过 Annexin V/碘化丙啶双重染色分析细胞凋亡。通过 Western blot 定量测定裂解的 caspase-3/多聚 ADP-核糖聚合酶和凋亡相关因子。通过实时聚合酶链反应测定 microRNAs (miRs) 的相对表达。
丹参酮 IIA 处理诱导 TOV-21G 细胞发生明显的细胞凋亡。丹参酮抑制生存素表达，而不影响 Bax、Bcl-2 和 Bcl-xL。我们进一步预测并通过实验证实 miR-205 在 TOV-21G 中的过表达，其外源性显著抑制生存素并促进细胞凋亡。miR-205 特异性拮抗剂完全阻断了丹参酮 IIA 的细胞抑制作用。
我们的数据表明，丹参酮 IIA 通过直接上调 miR-205 诱导卵巢癌 TOV-21G 细胞发生细胞凋亡。我们的研究强调了丹参酮 IIA 治疗卵巢恶性肿瘤的潜在应用。
