The Natural Flavonoid Pectolinarigenin Targets On-Canonical NF-κB Pathway to Inhibit Esophageal Squamous Cell Carcinoma and Enhances Paclitaxel Efficacy.

Pectolinarigenin (PEC) is a natural flavonoid compound derived from Chinese herbal medicines. Previous studies have demonstrated its significant inhibitory effects against various malignancies. However, the effect and molecular mechanism of PEC in esophageal squamous cell carcinoma (ESCC) as well as its potential for combination with clinical chemotherapeutics for ESCC treatment is still obscure. Here, we systematically explored the anti-ESCC effects of PEC, elucidated its molecular mechanism, and evaluated its synergistic therapeutic potential with paclitaxel (PTX), a first-line chemotherapeutic agent for ESCC. The results showed that PEC obviously restrained proliferation and migration, and induced apoptosis of ESCC cells. Mechanistically, we found that PEC targets the non-canonical pathway of NF-κB, specifically preventing nuclear translocation of p52 and RELB, thus suppressing the transcriptional activity of this pathway. Moreover, we confirmed that PEC markedly inhibited tumor growth and exhibited a strong synergistic effect on the progression of ESCC when combined with PTX using a xenograft model of nude mice. Our research results have revealed a new molecular mechanism for the anti-ESCC efficiency of PEC. This study highlights PEC potential as a promising candidate for ESCC monotherapy or combination therapy with PTX and points out a new strategy for the clinical treatment of natural flavonoids to ESCC.