Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo

Author:

Xie Jianhao12,Wu Shengjie12,Liao Wenfeng1,Ning Jingru13,Ding Kan124ORCID

Affiliation:

1. Carbohydrate-Based Drug Research Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Rd, Pudong New district, Shanghai 201203 , China

2. University of Chinese Academy of Sciences , No. 19(A) Yuquan Road, Beijing 100049 , China

3. School of Chinese Materia Medica, Nanjing University of Chinese Medicine , 138 Xianlin Rd, Qixia District, Nanjing 210023 , China

4. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Science, SSIP Healthcare and Medicine Demonstration Zone , Zhongshan Tsuihang New District, Zhongshan, Guangdong 528400 , China

Abstract

Abstract 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.

Funder

Lingang Laboratory

Shanghai Municipal Science and Technology Major Project

National Natural Science Foundation of China

Zhongshan Municipal Bureau of Science and Technology

Publisher

Oxford University Press (OUP)

Subject

Biochemistry

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