RQ43: A quinoline derivative that inhibits pancreatic cancer cell EMT and migration

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to early metastasis and therapeutic resistance. The epithelial-to-mesenchymal transition (EMT) drives PDAC invasiveness and poor prognosis. RQ-43, a novel quinoline derivative, has shown antiproliferative activity in other cancer models previously with unclear mechanisms. This study investigated its cytotoxic, anti-migratory/invasive effects, and mechanisms of action in PDAC. Methods: Human (PANC1) and murine (PAN02) PDAC cell lines were treated with RQ-43 (0.625-20 µM) for 48 h, and cell viability measured by MTT assay. Migration and invasion were assessed using wound-healing and Boyden chamber assays at sub-cytotoxic drug concentrations. EMT-related genes and transcription factors were assessed by qPCR. A syngeneic orthotopic PDAC mouse model was used to assess the in vivo effects of RQ-43 in C57/BL/6 mice. Results: RQ-43 selectively decreased PDAC cell viability in a dose-dependent manner with IC₅₀ values of 3.61 µM (PANC1) and 8.24 µM (PAN02). At concentrations of 2.5 µM for PANC1 and 5-20 µM for PAN02, RQ-43 significantly inhibited migration, reducing wound closure by 27.5% in PANC1 and 78% in PAN02 (p < 0.05 compared to controls). Invasion through Matrigel-coated Boyden chamber was also significantly suppressed in both cell lines (p < 0.01). EMT-related transcription factors Snail and B-catenin were downregulated (p < 0.05). In the orthotopic model, RQ-43 treatment (80 mg/kg, daily IP) significantly reduced tumour weight by 62.95% compared with controls. Metastasis rate was 80% in the control group and 25% in the treated group. Conclusions: RQ-43 demonstrates cytotoxic, anti-migratory/invasive effects in vitro and effectively reduces tumour growth and metastasis in vivo. EMT-related transcription factors were downregulated. Further efficacy and mechanistic evaluation are warranted.