Department of Orthopedics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Orthopedic Surgery, The Fifth Hospital of Harbin, Harbin, China.
Biosci Rep. 2019 Jan 15;39(1). doi: 10.1042/BSR20181707. Print 2019 Jan 31.
Osteosarcoma (OS) is the most common malignant neoplasm in children and adolescents with a very high propensity for local invasion and poor response to current therapy. Anti-cancer effect of chamaejasmine is newly discovered from Stellera chamaejasmine L. Our study focuses on investigating the effect of chamaejasmine on the cellular apoptosis, proliferation, autophagy, and the underlying mechanisms in MG-63.
Our study investigated the concentration of chamaejasmine in MG-63 cells by MTT and verified that chamaejasmine inhibited cell invasion by transwell. We also used Hoechst staining as well as apoptotic associated-proteins in MG-63 cells. Meanwhile, we also detected the lysophagesome and autophagsome by Lysotracker. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) knockdown was performed with siRNA.
Our results show that chamaejasmine exerts cellular growth inhibition, pro-apoptotic and pro-autophagic effect via activating AMPK in MG-63 cells. Furthermore, chamaejasmine significantly increases autophagic cell via the inhibition of mammalian target of rapamycin (mTOR) and activation of AMPK signaling pathways. Administrated with chamaejasmine also induces reactive oxygen species (ROS) generation, indicating cross-talking between these two primary modes of programmed cell death.
Our results show that chamaejasmine promotes apoptosis and autophagy by activating AMPK/mTOR signaling pathways with involvement of ROS in MG-63 cells. Chamaejasmine is a promising anti-cancer agent in OS treatment, and further studies are needed to confirm its efficacy and safety or other cancer cells.
骨肉瘤(OS)是儿童和青少年中最常见的恶性肿瘤,具有很高的局部侵袭性和对当前治疗反应不佳的倾向。从蛇婆子中发现了蛇婆子素的抗癌作用。我们的研究重点是研究蛇婆子素对 MG-63 细胞中细胞凋亡、增殖、自噬的影响及其潜在机制。
本研究通过 MTT 法检测 MG-63 细胞中蛇婆子素的浓度,并通过transwell 实验验证蛇婆子素抑制细胞侵袭。我们还使用 Hoechst 染色以及凋亡相关蛋白检测 MG-63 细胞中的凋亡。同时,我们还通过 Lysotracker 检测溶酶体和自噬体。采用 siRNA 进行腺苷 5'-单磷酸(AMP)激活的蛋白激酶(AMPK)敲低。
我们的结果表明,蛇婆子素通过激活 MG-63 细胞中的 AMPK,发挥细胞生长抑制、促凋亡和促自噬作用。此外,蛇婆子素通过抑制哺乳动物雷帕霉素靶蛋白(mTOR)和激活 AMPK 信号通路,显著增加自噬细胞。给予蛇婆子素还会诱导活性氧(ROS)的产生,表明这两种程序性细胞死亡的主要模式之间存在交叉对话。
我们的结果表明,蛇婆子素通过激活 AMPK/mTOR 信号通路,同时涉及 ROS,促进 MG-63 细胞中的凋亡和自噬。蛇婆子素是治疗骨肉瘤的一种很有前途的抗癌药物,需要进一步的研究来确认其疗效和安全性或其他癌细胞。