Obesity associated elevated leptin might contribute to paclitaxel resistance via PLCB1/IP3R1 axis in head and neck cancers.

BACKGROUND: Head and neck cancer (HNC) is a heterogeneous malignancy with limited therapeutic success, largely due to its complex pathogenesis and high chemoresistance. Paclitaxel is commonly used in HNC therapy; however, the frequent development of resistance reduces its efficacy. Obesity has been linked to cancer progression, and leptin, an adipokine elevated in obesity, has emerged as a potential mediator of treatment resistance. METHODS: To explore leptin's role in paclitaxel resistance, taxol-resistant HNC cell lines were treated with leptin. Tumor tissues from obese and non-obese HNC patients were examined by immunohistochemistry to evaluate leptin, phospholipase C beta 1 (PLCB1), and inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) expression. The effect of PLCB1 inhibition on IP3R1 expression, apoptosis, and cell viability was analyzed using functional assays. RESULTS: Leptin treatment enhanced paclitaxel resistance and modulated the PLCB1-IP3R1 signaling pathway in HNC cells. Pharmacological inhibition of PLCB1 increased IP3R1 expression, promoted apoptosis, and decreased cell viability. CONCLUSION: Leptin contributes to paclitaxel resistance in HNC through activation of the PLCB1/IP3R1 axis. Targeting this signaling pathway may represent a promising therapeutic approach to overcome chemoresistance, particularly in obese patients with HNC.