SKN

Pazopanib and Hyperthermia Synergistically Inhibit LMS Cell Proliferation by Inducing Apoptosis

Uterine leiomyosarcoma (LMS) is a rare, aggressive malignancy resistant to chemotherapy and radiotherapy. Pazopanib, a multitargeted tyrosine kinase inhibitor, is approved for advanced soft-tissue sarcomas but shows limited overall survival benefit. Regional hyperthermia (40-43°C) combined with chemotherapy reduces recurrence and mortality in high-risk soft-tissue sarcoma. Lin et al. investigated whether hyperthermia synergizes with pazopanib against LMS growth and explores underlying molecular mechanisms.

They initially identified the optimal hyperthermia protocol for uterine leiomyosarcoma (LMS) cells. Exposure to 42°C for 2 h did not induce cell death but maximized membrane permeability as shown by calcein AM assay. Dose-response curves for pazopanib under different conditions. SKLMS-1 cells treated with pazopanib and/or hyperthermia (42°C, 2 h) showed markedly reduced proliferation with combined treatment versus either alone (Fig. 1a). Hyperthermia alone increased calcein AM entry (Fig. 1b, c). Combined treatment synergistically induced apoptosis, evidenced by cleaved PARP levels exceeding the sum of individual treatments at 72 h in both SKLMS-1 and SKN cells (Fig. 1d). These data support apoptosis as the mechanism underlying pazopanib- and hyperthermia-induced LMS growth inhibition.