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Obesity associated elevated leptin might contribute to paclitaxel resistance via PLCB1/IP3R1 axis in head and neck
Fatma Sanli1, Betul Gundogdu2, Omer Faruk Karatas1
1Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkiye; Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkiye.
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.
