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.