Sun Yuanjue, Liu Liguo, Wang Yaling, He Aina, Hu Haiyan, Zhang Jianjun, Han Mingyong, Huang Yujing
Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 250021, Shandong, People's Republic of China,
Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China.
Onco Targets Ther. 2019 Mar 15;12:2011-2021. doi: 10.2147/OTT.S172909. eCollection 2019.
The aims of this study were to determine the effect of curcumin on osteosarcoma (OS) cells due to inactivation of the p-JAK2/p-STAT3 pathway and evaluate the prognostic value of this pathway in OS.
We exposed a human OS cell line (MG-63) to different concentrations of curcumin. Then, we characterized the effects on MG-63 cells using assays (cell viability, colony formation, cell cycle, wound healing, invasion), flow cytometry, Western blot, immunohistochemical analyses, and tumor xenograft.
The half-maximal inhibitory of curcumin for MG-63 cells at 24 hours was 27.6 µM. The number of colonies of MG-63 cells was decreased obviously upon curcumin (10 and 20 µM) treatment. We also found increased accumulation of MG-63 cells in the G2/M phase upon curcumin (10 and 20 µM) treatment. Apoptosis was increased in 10 and 20 µM curcumin-treated MG-63 cells. After incubation of physically wounded cells for 24 hours, the percentage wound width increased upon curcumin exposure. Curcumin obviously decreased the expression of pJAK-2 and pSTAT-3 in MG-63 cells in a dose-dependent manner. Curcumin dose-dependently inhibited the proliferation, migration, and invasion of MG-63 cells and induced arrest of the G0/G1 phase and apoptosis by inhibiting the p-JAK2/p-STAT3 pathway. The linear correlativity between expression of p-JAK2 and STAT3 was very prominent, and both were closely associated with lung metastasis. In vivo study suggested that curcumin suppressed tumor growth through JAK2/STAT3 signaling.
Curcumin-mediated inhibition of the proliferation and migration of MG-63 cells was associated with inactivation of JAK/STAT signaling.
本研究旨在确定姜黄素因p-JAK2/p-STAT3信号通路失活对骨肉瘤（OS）细胞的影响，并评估该信号通路在骨肉瘤中的预后价值。
我们将人骨肉瘤细胞系（MG-63）暴露于不同浓度的姜黄素中。然后，我们通过实验（细胞活力、集落形成、细胞周期、伤口愈合、侵袭）、流式细胞术、蛋白质免疫印迹、免疫组织化学分析和肿瘤异种移植来表征对MG-63细胞的影响。
姜黄素在24小时对MG-63细胞的半数最大抑制浓度为27.6μM。姜黄素（10和20μM）处理后，MG-63细胞的集落数量明显减少。我们还发现姜黄素（10和20μM）处理后MG-63细胞在G2/M期的积累增加。10和20μM姜黄素处理的MG-63细胞凋亡增加。对物理损伤细胞孵育24小时后，姜黄素处理后伤口宽度百分比增加。姜黄素以剂量依赖性方式明显降低MG-63细胞中pJAK-2和pSTAT-3的表达。姜黄素通过抑制p-JAK2/p-STAT3信号通路剂量依赖性地抑制MG-63细胞的增殖、迁移和侵袭，并诱导G0/G1期阻滞和凋亡。p-JAK2和STAT3表达之间的线性相关性非常显著，且两者均与肺转移密切相关。体内研究表明姜黄素通过JAK2/STAT3信号通路抑制肿瘤生长。
姜黄素介导的对MG-63细胞增殖和迁移的抑制与JAK/STAT信号通路失活有关。
