Title:Morusin Suppresses Pancreatic Cancer Cell Proliferation and Migration by Targeting SLC6A12 to Inhibit NF-κB and β-catenin Signaling Pathways
Volume: 21
Issue: 2
Author(s): Wenyan Yang, Wei Zhu, Zhiyang Yao, Zhao Wang, Shengzhi Liu, Xiaoqing Guan*Jiang-Jiang Qin*
Affiliation:
- Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China
- Center for Innovative Drug Research, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou,
Zhejiang, 310018, China
- Key Laboratory for Molecular Medicine and Chinese Medicine Preparations, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310018, China
Keywords:
Morusin, pancreatic cancer, SLC6A12, NF-κB, β-catenin, proliferation.
Abstract:
Introduction: Pancreatic cancer is characterized by a poor prognosis and low survival
rate, underscoring the urgent need for the development and optimization of novel therapeutic
interventions. Morusin has been reported to have anticancer activity in a variety of cancers.
Therefore, the present study aimed to elucidate the anticancer effects and potential mechanisms
of Morusin in pancreatic cancer.
Methods: We evaluated the anticancer effect of Morusin in pancreatic cancer cells, including its
impact on pancreatic cancer cell proliferation, colony formation potential, migration, invasion,
cell cycle and apoptosis. RNA sequencing (RNA-seq) analysis was employed to identify potential
genes involved in the anticancer activity of Morusin. Furthermore, RT-qPCR and Western
blot analysis were utilized to verify the findings.
Results: Our results demonstrated that Morusin administration significantly impaired cell
proliferation, migration and invasive activity of pancreatic cancer cells. Additionally, Morusin
induced apoptosis and disrupted cell cycle progression. Importantly, Morusin was found to
co-regulate SLC6A12, HSPA2, P2RY6 and JPH2 in both cell lines by RNA-seq analysis,
with the most significant decrease in mRNA levels of SLC6A12 following administration.
Mechanistically, Morusin was found to regulate the expression of SLC6A12 and inhibit NF-κB
and β-catenin signaling pathways, which may represent the underlying mechanisms of its antitumor
activity.
Conclusion: Our findings suggest that Morusin holds potential as an anti-pancreatic cancer
agent by targeting SLC6A12 and modulating its associated signaling pathways.
