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.

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

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.

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.

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.

Endoplasmic reticulum stress (ERS) and epithelial‑mesenchymal transition (EMT) have important roles in fibrosis and tumour development. Moderate ERS activates cellular defence mechanisms in response to noxious stimuli; however, sustained or overly strong ERS induces apoptosis. In this disease process, EMT induces epithelial cells to acquire the ability to migrate and invade. Reportedly, ERS directly or indirectly regulates EMT processes through multiple mechanisms (such as key transcription factors, signalling pathways, ferroptosis, autophagy and oxidative stress), and both processes form a complex network of interactions. Given the critical roles of ERS and EMT in disease, targeted intervention of these two processes has emerged as a potential therapeutic strategy. In the present study, the molecular interaction mechanism of ERS and EMT was systematically explored, research progress in fibrotic and neoplastic diseases was reviewed and the potential application prospects of related targeted therapies were examined, which may provide new ideas for the development of drugs to reverse fibrosis and treat tumours.

Ca2+, as critical second messengers in biological processes, plays a pivotal role in the regulation of diverse cellular signaling pathways. The dysregulation of calcium signaling is intricately linked to the progression of various cancers. The capacity of Ca2+ to modulate cell death and proliferation, along with its potential for pharmacological manipulation, presents a promising avenue for the development of novel cancer therapeutics. This review provides a comprehensive overview of the classification of Ca2+ channels and their mechanisms of action in oncogenesis, explores the application of Ca2+ blockers in cancer treatment, and underscores the importance of conducting further clinical trials.

The causes of death in patients with advanced esophageal cancer are multifactorial, with tumor metastasis being one of the important factors. Histone acetylation promotes the migration of esophageal squamous cell carcinoma (ESCC) cells, while the histone deacetylase inhibitor (HDACi) shows complex effects on tumor functions.

To comprehensively elucidate the impact and molecular mechanisms of trichostatin A (TSA), an HDACi, on cell migration in ESCC through bromodomain-containing protein (BRD4)/cellular myelocytomatosis oncogene (c-Myc)/endoplasmic reticulum (ER)-stress.

The effects of TSA on ESCC cell lines Eca109 and EC9706 migration were evaluated using Transwell assays, with small interfering transfection and pathway-specific inhibitors to elucidate underlying mechanisms. The mRNA levels involved were examined by quantitative real-time polymerase chain reaction. Protein levels of acetylated histones H3 (acH3) and acetylated histones H4, BRD4, c-Myc, as well as markers of ER stress and epithelial-mesenchymal transition (EMT), were analyzed using western blot. Additionally, this method was also used to examine acH3 levels in esophageal cancer tissues and adjacent tissues. Patient outcomes were subsequently tracked to identify prognostic indicators using Log-Rank tests and Cox multivariate analysis.

TSA promoted the migration of ESCC cells by stimulating the EMT process. TSA-mediated histone acetylation facilitated the recruitment of BRD4, a bromodomain-containing protein, triggering the expression of c-Myc. This cascade induced ER stress and enhanced EMT in ESCC cells. To further elucidate the underlying mechanism, we employed various interventions including the ER stress inhibitor 4-phenylbutyric acid, knockdown of c-Myc and BRD4 expression, and utilization of the BRD4 inhibitor carboxylic acid as well as the inhibitor of TSA 1. Mechanistically, these studies revealed that TSA-mediated histone acetylation facilitated the recruitment of BRD4, which in turn triggered the expression of c-Myc. This sequential activation induced ER stress and subsequently enhanced EMT, thereby promoting the migration of ESCC cells. Additionally, we examined histone acetylation levels in specimens from 43 patients with ESCC, including both tumor tissues and paired adjacent tissues. Statistical analysis unveiled a negative correlation between the level of histone acetylation and the long-term prognosis of patients with ESCC.

TSA promoted ESCC cell migration through the BRD4/c-Myc/ER stress pathway. Moreover, elevated histone acetylation in ESCC tissues correlated with poor ESCC prognosis. These findings enhance our understanding of ESCC migration and HDACi therapy.

Calcium ion dysregulation exerts profound effects on various physiological activities such as tumor proliferation, migration, and drug resistance. Calcium-related channels play a regulatory role in maintaining calcium ion homeostasis, with most channels being highly expressed in tumor cells. Additionally, these channels serve as potential drug targets for the development of antitumor medications. In this review, we first discuss the current research status of these pathways, examining how they modulate various tumor functions such as epithelial-mesenchymal transition (EMT), metabolism, and drug resistance. Simultaneously, we summarize the recent progress in the study of novel small-molecule drugs over the past 5 years and their current status.