EFFECT OF SEVOFLURANE ON MIGRATION AND INVASION OF CERVICAL CANCER CELLS IN RATS BY REGULATING HIPPO-YAP/TAZ SIGNALING

This research set out to explore how sevoflurane anesthesia modulates the migratory and invasive capacities of cervical cancer cells in rats through the regulation of the Hippo-YAP/TAZ signaling pathway, providing experimental evidence for optimizing anesthetic management in cervical cancer surgery. One hundred female Sprague-Dawley rats were randomly divided into the five groups (n=20 per group): Control group (no intervention), SEV group (2% sevoflurane+1×10⁶ HeLa cells), N-SEV group (4% isoflurane +1×10⁶ HeLa cells), BAY593 group (4% isoflurane +10 mg/kg BAY593+1×10⁶ HeLa cells), and SEV+BAY593 group (2% sevoflurane+10 mg/kg BAY593+1×10⁶ HeLa cells). The tumor volume was monitored; Transwell and wound healing tests were carried out to evaluate cell invasion and migration respectively; and RT-PCR, ELISA, and Western blotting were adopted to detect the expression of pathway-related molecules. On postoperative day 28, the tumor volume in the SEV group (1.75±0.22 cm³) was significantly larger than that in the BAY593 group (0.65±0.12 cm³) (P≤0.001). Compared with the N-SEV group, the SEV group experienced marked body weight loss alongside prominent tumor enlargement. Meanwhile, tissue levels of YAP, TAZ, and Vimentin at both protein and transcript levels were markedly elevated, while p-YAP and E-cadherin protein abundances were substantially suppressed. Cell migration rate and the number of invasive cells were also significantly increased (P ≤ 0.05). Relative to the SEV group, animals receiving combined SEV + BAY593 treatment displayed obvious shrinkage of tumor lesions, alleviated body weight decline, remarkable suppression of YAP, TAZ, and Vimentin levels, restored p-YAP and E-cadherin abundance, as well as robustly restrained cell migration and invasion capacity (P ≤ 0.05). No obvious disparities were detected between the SEV + BAY593 group and the N-SEV group regarding tumor volume, cell migration rate, invasive cell count, or the abundance of all core molecular markers (P > 0.05). Sevoflurane anesthesia can significantly boost the migratory capacity, invasive potential and neoplastic proliferation of cervical carcinoma cells derived from rats by activating the Hippo-YAP/TAZ signaling pathway. Treatment with the YAP/TAZ pathway inhibitor BAY593 effectively blocks this effect and completely reverses the tumor-promoting effect of sevoflurane. These findings suggest that, in cervical cancer surgery, intervention targeting this pathway or selection of an alternative anesthesia regimen may help optimize anesthesia management and improve prognosis. Keywords: sevoflurane; cervical cancer; Hippo-YAP/TAZ pathway; tumor volume; migration