Src是甘露糖对于体外和体内胰腺癌细胞生长的靶分子。
Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo.
发表日期:2023 Sep 02
作者:
Jianhao Xie, Shengjie Wu, Wenfeng Liao, Jingru Ning, Kan Ding
来源:
Cell Death & Disease
摘要:
胰腺导管腺癌(PDAC)是一种高度恶性的癌症,治疗选择有限。曼齐糖(Mannose)是一种常见的单糖,通过与葡萄糖相同的转运蛋白在细胞内摄取,已被证明在多种癌症中,包括PDAC中诱导生长阻滞并增强化疗诱导的细胞死亡。然而,曼齐糖在PDAC中的分子靶点和作用机制尚不明确。本研究采用网络药理学、生物信息学分析和实验证实的综合方法,研究了曼齐糖在PDAC中的药理靶点和作用机制。我们的结果表明,蛋白质Src是曼齐糖在PDAC中的关键靶点。此外,计算分析揭示了曼齐糖是一种高溶解度化合物,符合Lipinski法则,其靶标分子的表达与PDAC患者的生存率和预后相关。最后,我们通过体外和体内实验证实了我们的发现。总之,我们的研究提供了曼齐糖通过作用于Src抑制PDAC生长的证据,暗示其可能是PDAC的一种有希望的治疗候选药物。© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose's action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski's rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.