Wu Jian, Lu Wen-Ying, Cui Lei-Lei
Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, Jiangsu, China E-mail :
Asian Pac J Cancer Prev. 2015;16(7):2813-8. doi: 10.7314/apjcp.2015.16.7.2813.
To investigate the regulatory effect of curcumin on expression of signal transducer and activator of transcription 3 (STAT3) in skin squamous cell carcinoma tissues as well as possible mechanisms of curcumin in prevention and treatment of skin squamous cell carcinoma.
Highly invasive A431 cells were treated with curcumin at various doses .The cytotoxic effects of treatment with 5, 10, 15, 20, 25, 30, 35, 40 and 50 umol/L curcumin for 24, 48 and 72 hours on A431 cells were measured by MTT assay. The invasion capacity of cells treated with 5, 10 and 15 umol/L curcumin was measured by Transwell test, while adhesive ability was assessed by cell adhesion assay. The effects of 5,10 and 15 umol/L curcumin on expression levels of STAT3 were determined by Western blotting and on transcription levels of STAT3 mRNA by RT-PCR.
Treatment with curcumin at a doses of more than 15 umol/L for more than 24 hour inhibited the growth of A431 cells in a time-and dose-dependent fashion (p<0.001). The doses of 15 umol/L and less for 24 hours showed no significant cytotoxic effects on the cells, survival rates being more than 85%.The invasion and adhesive abilities decreased gradually with the increasing curcumin concentration, 15 umol/L exerting the strongest inhibitory effects (p<0.05). Curcumin showed significant dose-dependent inhibitory effects on the transcription level of STAT3 mRNA (p<0.05).
Curcumin may reduce the invasive ability of A431 cells by inhibiting the activation of STAT3 signal pathway and expression of STAT3 as a target gene in the pathway.
探讨姜黄素对皮肤鳞状细胞癌组织中信号转导子和转录激活子3(STAT3)表达的调控作用以及姜黄素防治皮肤鳞状细胞癌的可能机制。
用不同剂量的姜黄素处理高侵袭性A431细胞。采用MTT法检测5、10、15、20、25、30、35、40和50 μmol/L姜黄素处理24、48和72小时对A431细胞的细胞毒性作用。采用Transwell试验检测5、10和15 μmol/L姜黄素处理的细胞的侵袭能力,同时通过细胞黏附试验评估黏附能力。采用蛋白质印迹法测定5、10和15 μmol/L姜黄素对STAT3表达水平的影响,采用逆转录-聚合酶链反应(RT-PCR)测定对STAT3 mRNA转录水平的影响。
剂量超过15 μmol/L的姜黄素处理超过24小时可抑制A431细胞的生长,呈时间和剂量依赖性(p<0.001)。15 μmol/L及以下剂量处理24小时对细胞无明显细胞毒性作用,存活率超过85%。侵袭和黏附能力随姜黄素浓度增加而逐渐降低,15 μmol/L时抑制作用最强(p<0.05)。姜黄素对STAT3 mRNA转录水平具有显著的剂量依赖性抑制作用(p<0.05)。
姜黄素可能通过抑制STAT3信号通路的激活及该通路中靶基因STAT3的表达来降低A431细胞的侵袭能力。