Tanshinone IIA Inhibits Proliferation and Induces Apoptosis Through the Downregulation of Survivin in Keloid Fibroblasts
Tanshinone IIA Inhibits Proliferation and Induces Apoptosis Through the Downregulation of Survivin in Keloid Fibroblasts
复制标题
DOI：
10.1097/sap.0000000000000544
复制
发表时间：
2016-02-01
影响因子：
1.5
通讯作者：
Liu, Dalie
中科院分区：
文献类型：
--
作者：
Chen, Gang;Liang, Yimin;Liu, Dalie
瘢痕疙瘩被认为是良性皮肤纤维增生性肿瘤。瘢痕疙瘩成纤维细胞（KFs）持续增殖，不能进行细胞凋亡，没有治疗是完全有效的对这些病变。丹参酮IIA可诱导多种肿瘤细胞凋亡并抑制其增殖。在这项研究中，我们研究了丹参酮IIA对KFs增殖，细胞周期和凋亡的调节作用，并探讨了可能的机制。首先，用不同浓度的丹参酮IIA处理KFs和正常皮肤成纤维细胞（NSFs）。采用CCK-8法检测KFs和NSFs的增殖活性，流式细胞仪检测KFs细胞周期和凋亡情况。丹参酮Ⅱ A处理72小时后，KFs的增殖能力明显下降（P < 0.001）。此外，与KFs相比，丹参酮IIA处理的NSFs没有表现出明显的效果。丹参酮IIA处理72 h后，各组KFs中G 0/G1期细胞比例均显著增加（P < 0.001）。丹参酮IIA作用120 h后，KFs中早期凋亡细胞的比例明显增加（P < 0.001）。凋亡抗体芯片和Western blot分析显示丹参酮IIA降低KFs中survivin的表达（P < 0.001）。总之，丹参酮IIA下调生存素和失活KFs，从而表明丹参酮IIA可以作为一个潜在的临床瘢痕疙瘩治疗。
Keloids are considered benign dermal fibroproliferative tumors. Keloid fibroblasts (KFs) persistently proliferate and fail to undergo apoptosis, and no treatment is completely effective against these lesions. Tanshinone IIA induces apoptosis and inhibits the proliferation of various tumor cell types. In this study, we investigated the effect of tanshinone IIA on the regulation of proliferation, cell cycle, and apoptosis in KFs, and investigated potential mechanisms involved in the effects. First, KFs and normal skin fibroblasts (NSFs) were treated with various concentrations of tanshinone IIA. Cell counting kit-8 (CCK-8) was used to assess the proliferative activity of KFs and NSFs, and flow cytometry was used to investigate the cell cycle and apoptosis in KFs. We found that the proliferation of all tanshinone IIA-treated KFs was significantly decreased after treatment for 72 hours (P < 0.001). Also, NSFs treated with tanshinone IIA did not exhibit noticeable effects compared with KFs. In addition, the percentages of G0/G1 cells in all tanshinone IIA-treated KFs were significantly increased after treatment for 72 hours (P < 0.001). And the percentages of cells undergoing early apoptosis in all tanshinone IIA-treated KFs were significantly increased after treatment for 120 hours (P < 0.001). Furthermore, the apoptosis antibody array kit and Western blot analysis revealed that tanshinone IIA decreased survivin expression in KFs (P < 0.001). In conclusion, tanshinone IIA downregulates survivin and deactivates KFs, thus suggesting that tanshinone IIA could serve as a potential clinical keloid treatment.