2. Academic Validation
  3. Rosuvastatin inhibits carcinogenesis through Ca2+ triggered endoplasmic reticulum stress pathway in pancreatic cancer

Rosuvastatin inhibits carcinogenesis through Ca2+ triggered endoplasmic reticulum stress pathway in pancreatic cancer

  • Cell Signal. 2025 Mar 17:131:111753. doi: 10.1016/j.cellsig.2025.111753.
Hui Miao 1,  Baojian Zhang 2,  Yue Li 2,  Xiao Ma 2,  Yang Yang 3,  Zhenhua Lin 2,  Yanqun Liu 4
Affiliations

Affiliations

  • 1 Central Laboratory, Yanbian University Hospital, Yanji 133000, China; Dunhua City Hospital, Dunhua 133700, China.
  • 2 Central Laboratory, Yanbian University Hospital, Yanji 133000, China; Key Laboratory of Pathobiology (Yanbian University), State Ethnic Affairs Commission, Yanji 133002, China.
  • 3 Key Laboratory of Pathobiology (Yanbian University), State Ethnic Affairs Commission, Yanji 133002, China.
  • 4 Central Laboratory, Yanbian University Hospital, Yanji 133000, China; Key Laboratory of Pathobiology (Yanbian University), State Ethnic Affairs Commission, Yanji 133002, China. Electronic address: 13844312816@163.com.
PMID: 40107481 DOI: 10.1016/j.cellsig.2025.111753
Abstract

Background: Pancreatic Cancer remains one of the most challenging malignancies to treat due to its late-stage diagnosis, aggressive progression, and high resistance to existing therapies. Rosuvastatin (ROV), known for its hypolipidemic effects, which significantly inhibited clonogenic capacity and epithelial-mesenchymal transition (EMT) in prostate Cancer cells. However, the anti-cancer mechanisms of ROV in PC have not yet been fully explored.

Purpose: This study aimed to investigate the potential anti-cancer effects of ROV on PC cells and to elucidate the underlying mechanisms.

Methods: Cytotoxicity was detected via MTT assay, while epithelial-mesenchymal transition (EMT) markers, CA2+ levels, and endoplasmic reticulum (ER) stress were observed with fluorescence microscopy. RNA-seq analysis was used to identify significantly changed mRNA expression following ROV treatment. Additionally, western blotting and immunohistochemistry (IHC) were conducted to examine proteins involving in the cell cycle, EMT, CA2+ signaling, and endoplasmic reticulum stress (ERS) in vitro and in vivo.

Results: ROV inhibited PC cell proliferation by arresting the cell cycle at the G1/S phase and partially reducing cell mobility during the EMT process. A total of 1336 significantly different RNAs (P < 0.05 and |logFC|>1) were identified and analyzed through RNA-seq, revealing the CA2+ and ER pathways in PC cells treated with ROV. ROV treatment significantly altered the level of intracellular CA2+, triggering the ERS pathway and modulating the CA2+/CaM/CaMKII/ERK pathway. Furthermore, ROV inhibited key proteins within the CA2+ and ERS pathways, leading to reduced cell proliferation, mobility and G1/S phase arrest. In tumor tissues, the expression of Ki67, EMT markers, Calmodulin, and ATF6 corroborated the in vitro findings.

Conclusion: ROV inhibited proliferation and metastasis in PC cells by inhibiting the EMT process through the CA2+/CaM/CaMKII/ERK and CA2+-mediated ERS pathways, highlighting its potential as a prophylactic and therapeutic agent for PC.

Keywords

Calcium; Endoplasmic reticulum stress; Metastasis; Pancreatic cancer; Rosuvastatin.

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