Low-Dose Paclitaxel Combined with Dehydrocavidine Synergistically Suppresses Cervical Cancer by Inhibiting FASN/SCD1-Mediated Lipid Metabolism.

Abstract

Cervical cancer is a leading cause of cancer-related death among women, and acquired resistance to paclitaxel (PTX) frequently results in treatment failure. Dehydrocavidine (DHC), the principal bioactive alkaloid from the traditional Chinese herb Corydalis saxicola, has shown antitumor activity, but its potential in cervical cancer and synergism with PTX remain unknown. We investigated the combined effect of low-dose PTX and DHC in HeLa and SiHa cells and a HeLa xenograft model. ZIP (zero interaction potency) synergy analysis revealed strong synergy in inhibiting proliferation, colony formation, and migration. In vivo, the combination significantly suppressed xenograft tumor growth. Network pharmacology, molecular docking, and experimental validation identified fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) as key targets; the combination downregulated their expression, reducing lipid droplets and triglyceride accumulation. Public single-cell transcriptomic analysis showed elevated FASN/SCD1 in tumor cells and cancer-associated fibroblasts, correlating with poor overall survival. These findings demonstrate that low-dose PTX plus DHC synergistically suppresses cervical cancer by inhibiting FASN/SCD1-mediated lipid metabolism reprogramming, providing a promising strategy to overcome PTX resistance and reduce toxicity.