Palmaturbine Inhibits Pancreatic Ductal Adenocarcinoma by Suppressing the JAK2/STAT3 Signaling Pathway

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an extremely poor prognosis, and current clinical treatment options are limited. Natural products, due to their multi-target and low-toxicity characteristics, have emerged as an important direction for the development of anti-tumor drugs. Palmaturbine (Pal), an isoquinoline alkaloid derived from Coptis chinensis and Berberis species, has shown anti-inflammatory and anti-tumor potential in preliminary studies; however, its mechanism of action in PDAC remains unclear. This study systematically evaluated the anti-tumor effects and molecular mechanisms of Pal on PDAC through in vitro and in vivo experiments. In vitro, Pal significantly inhibited PDAC cell proliferation, migration, and invasion, induced G2/M phase cell cycle arrest, and promoted apoptosis. Transcriptomic sequencing and Western blot analysis revealed that Pal suppressed the JAK2/STAT3 signaling pathway by inhibiting the phosphorylation of JAK2 and STAT3. Animal experiments further indicated that Pal significantly inhibited the growth of subcutaneous xenograft tumors in nude mice without causing obvious toxicity. In summary, Pal, as a natural JAK/STAT pathway inhibitor, exhibits favorable anti-tumor activity and safety in PDAC treatment, holding potential as a novel candidate drug for PDAC.