Rhodiolin 通过人乳头状甲状腺癌中的糖酵解酶 GPI 抑制 PI3K/AKT/mTOR 信号通路。
Rhodiolin inhibits the PI3K/AKT/mTOR signaling pathway via the glycolytic enzyme GPI in human papillary thyroid cancer.
发表日期:2024 Jun 25
作者:
Jiaqiang Bo, Shuyu Mao, Jie Yang, Li Wang, Jia Zheng, Chunyu Zhang, Mingming Song, Siyu Chen, Chang Liu
来源:
PHYTOMEDICINE
摘要:
甲状腺乳头状癌(PTC)是一种头颈部内分泌恶性肿瘤。手术和化疗都是PTC的治疗方法,但都有副作用。探索用于 PTC 治疗的新型无毒抗 PTC 药物是一个未得到满足的需求。我们的目的是通过对特征良好的天然小分子库进行高通量筛选,以确定可以抑制 PTC 细胞增殖的抗 PTC 药物化合物。然后,通过体外细胞模型和异种移植肿瘤模型验证了红景天的抗PTC功能。结果:我们初步证明,红景天在体外和体内均能显着抑制PTC细胞的生长并诱导其凋亡。在代谢水平上,红景天素通过葡萄糖6-磷酸异构酶(GPI)阻断糖酵解,这表明糖酵解抑制可能参与介导红景天素的抗PTC功能。转录组学分析与生物信息学分析相结合,确定红景天治疗可抑制磷酸肌醇 3-激酶/蛋白激酶 B/哺乳动物雷帕霉素靶点 (PI3K/AKT/mTOR) 信号通路的磷酸化。总的来说,我们的研究结果表明,红景天素通过阻断糖酵解酶 GPI 的糖酵解,从而抑制 PI3K/Akt/mTOR 信号通路的磷酸化,从而抑制 PTC 细胞的增殖并诱导其凋亡。我们的研究表明,红景天素在抑制 PTC 细胞增殖和凋亡方面具有潜在用途。增殖并诱导 PTC 细胞凋亡。抑制GPI介导的PI3K/Akt/mTOR信号通路磷酸化在红景天的ant-PTC功能中发挥着极其重要的作用。这些结果表明红景天素是治疗 PTC 进展的一种有前景的药物。我们的研究结果从能量代谢的角度为PTC治疗提供了新的靶点和细胞信号通路,可为PTC治疗提供新的视角和新的药物选择。除此之外,我们的研究将有助于弥补 PTC 药物研究的不足。版权所有 © 2024 Elsevier GmbH。版权所有。
Papillary thyroid carcinoma (PTC) is an endocrine malignant tumor of the head and neck. Surgery and chemotherapy are PTC treatments, but have adverse effects. Exploration of new non-toxic anti-PTC drugs for PTC treatment is an unmet need.We aimed to identify anti-PTC drugs that could inhibit PTC-cell proliferation through high-throughput screening of a library of well-characterized naturally occurring small-molecule compounds. Then, the anti-PTC function of rhodiolin was validated by in vitro cell models and xenograft tumor models RESULTS: We initially demonstrated that rhodiolin inhibited the growth and induced the apoptosis of PTC cells significantly in vitro and in vivo. At the metabolic level, rhodiolin blocked glycolysis through glucose 6-phosphate isomerase (GPI), which suggested that glycolytic inhibition may be involved in mediating the anti-PTC function of rhodiolin. Transcriptomics analysis combined with bioinformatics analysis identified rhodiolin treatment to inhibit phosphorylation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Collectively, our findings demonstrated that rhodiolin inhibited the proliferation and induced the apoptosis of PTC cells by blocking glycolysis through the glycolytic enzyme GPI, thereby inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway.Our study demonstrates the potential use of rhodiolin in inhibiting the proliferation and inducing the apoptosis of PTC cells. Inhibition of phosphorylation of the PI3K/Akt/mTOR signaling pathway mediated by GPI plays an extremely important part in the ant-PTC function of rhodiolin. These results suggest that rhodiolin is a promising drug in the treatment of PTC progression. Our results provide a novel target and cell signaling pathway for PTC therapy from the perspective of energy metabolism, which could provide new perspectives and new drug choices for PTC therapy. In addition to that, our study will help to make up for the lack of drug research for PTC.Copyright © 2024 Elsevier GmbH. All rights reserved.