ReferenceID 6158
Rosmarinic Acid Decreases the Malignancy of Pancreatic Cancer Through Inhibiting Gli1 Signaling
Phytomedicine
BACKGROUND: Rosmarinic acid (RA) has been shown to exert anti-tumor effects on various types of cancer. However, its roles in the treatment of pancreatic ductal adenocarcinoma (PDAC) and the underlying mechanisms remain
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Record Fields
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- Reference Id
- 6158
- Evidence Id
- 22748
- Core Evidence Id
- 22748
- Source Reference Id
- 5577
- Herb2 Reference Id
- HBREF006374
- Subject Paper Key
- HBIN042438_34864627
- Pubmed Id
- 34864627
- Doi
- 10.1016/j.phymed.2021.153861
- Paper Title
- Rosmarinic Acid Decreases the Malignancy of Pancreatic Cancer Through Inhibiting Gli1 Signaling
- Paper Abstract
- BACKGROUND: Rosmarinic acid (RA) has been shown to exert anti-tumor effects on various types of cancer. However, its roles in the treatment of pancreatic ductal adenocarcinoma (PDAC) and the underlying mechanisms remain elusive. PURPOSE: The present study aimed to investigate the therapeutic effects of RA on PDAC as well as the underlying mechanisms. STUDY DESIGN: Evaluation of the effects of RA on PDAC malignancy both in vitro and in vivo. METHODS: Cell counting kit 8 (CCK8) assay, colony formation assay, 5-Ethynyl-2'-deoxyuridine (EDU) incorporation assay, cell cycle analysis, and apoptosis assay were conducted to assess the inhibitory effect of RA on PDAC cell proliferation. Meanwhile, western blotting and RT-qPCR assay were performed to detect the target gene expression at protein and mRNA levels, respectively. Moreover, the in vivo anti-tumor activities of RA were assayed in an xenograft mouse model of PDAC. RESULTS: RA dramatically down-regulated Gli1 and its downstream targets. Further studies showed that RA prevents the nuclear translocation of Gli1, while promoting the degradation of cytosolic Gli1 via the proteasome pathway. Moreover, we observed that RA induced G1/S cell cycle arrest and apoptosis in the PDAC cells through regulating the expression of P21, P27, CDK2, Cyclin E, Bax, and Bcl-2, it inhibited the PDAC cell migration and invasion via E-cadherin and MMP-9. Notably, Gli1 overexpression markedly reversed the above RA-induced effects on PDAC cells, whereas Gli1 knockdown enhanced the effects. Additionally, the in vivo assays demonstrated that RA suppresses the tumor growth of PDAC presumably by inhibiting Gli1. CONCLUSION: We provided evidence that RA restrained the nuclear translocation of Gli1 and facilitates Gli1 degradation via proteasome pathway, reducing the malignancy of PDAC cells. These findings implicated RA as a therapeutic agent for PDAC.
- Journal
- Phytomedicine
- Publish Year
- 2022
- Experiment Subject
- mouse
- Experiment Type
- Cell Experiment
- Phenotype Related
- Pancreatic Ductal Adenocarcinoma; Tumor; Pdac Malignancy; Cancer
- Paper Title Cn
- Paper Title En
- Rosmarinic Acid Decreases the Malignancy of Pancreatic Cancer Through Inhibiting Gli1 Signaling
- Bilingual Status
- semi_complete