title: Tanshinone IIA Inhibits Proliferation and Induces Apoptosis Through the Downregulation of Survivin in Keloid Fibroblasts.
abstract: 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.
authors.affiliation: From the *Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangdong; and †Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Yimin
authors.initials: Y
authors.lastname: Liang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Li
authors.forename: Dalie
authors.initials: D
authors.lastname: Liu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007627:Keloid / Q000188:drug therapy*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C021751:tanshinone