Cisplatin combined with high-intensity focused ultrasound inhibits endometrial cancer progression by inducing pyroptosis.

BACKGROUND

Cisplatin-based chemotherapy is limited by toxicity and resistance.High-intensity focused ultrasound (HIFU) is a noninvasive ablation technique with potential to enhance chemotherapy efficacy.

OBJECTIVE

To investigate the anti-tumor effects and mechanisms of cisplatin combined with HIFU in endometrial cancer.

METHODS

Safe cisplatin concentrations and HIFU parameters were screened in HEEpiC-SV40 cells. Proliferation, apoptosis, migration, and invasion of Ishikawa cells were assessed using CCK-8, EdU, colony formation, TUNEL, wound healing, and Transwell assays. Pyroptosis-related markers and PI3K/AKT pathway activity were evaluated by Western blot, qRT-PCR, and ELISA. Therapeutic efficacy was further examined in a nude mouse xenograft model.

RESULTS

Cisplatin (5 μg/mL) combined with HIFU (1 MHz, 160 J) was identified as the optimal treatment condition. The combination significantly inhibited Ishikawa cell proliferation, migration, and invasion while promoting pyroptosis. Mechanistically, combined treatment suppressed PI3K/AKT pathway activation and increased pyroptosis-related markers. These effects were reversed by the pyroptosis inhibitor AZL-N. Moreover, PI3K/AKT activation with 740 Y-P attenuated the anti-tumor and pyroptosis-inducing effects of the combination. In vivo, cisplatin combined with HIFU markedly restrained xenograft tumor growth and promoted tumor pyroptosis, whereas 740 Y-P pretreatment counteracted these effects.

CONCLUSIONS

Cisplatin combined with HIFU suppresses Type I endometrial cancer progression by inhibiting PI3K/AKT signaling and promoting pyroptosis, supporting its potential as a novel combination therapeutic strategy.