Thermally enhanced efficacy of chemotherapy potentiates cisplatin-based hyperthermic intraperitoneal chemotherapy in ovarian cancer.

Ovarian cancer is the deadliest gynecological malignancy, with high relapse and drug resistance rates. Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery and systemic chemotherapy has improved survival in patients with peritoneal metastases, though findings remain inconsistent. This study investigates whether the benefits of HIPEC are due to the additional chemotherapy or the combination with hyperthermia. High-grade and non-high-grade serous ovarian cancer cell lines were treated with carboplatin and paclitaxel. Additionally, the cells were treated with cisplatin at 37 to 43 °C for 90 min (HIPEC). Cell proliferation, colony formation, apoptosis, cell cycle and DNA damage were assessed by MTT, clonogenic assay, flow cytometry, western blot and γ-H2AX foci assay. High-grade serous cells were more sensitive to both carboplatin-paclitaxel and hyperthermia. Cisplatin demonstrated a temperature-dependent synergy with heat, resulting in increased DNA damage, apoptosis, and G2-arrest. Combining carboplatin and paclitaxel with hyperthermia plus cisplatin further reduced survival and increased cellular stress marker compared to carboplatin and paclitaxel alone. Hyperthermia significantly enhances cisplatin efficacy when added to carboplatin and paclitaxel pretreatment. This suggests that the addition of hyperthermia to cisplatin after carboplatin-paclitaxel is more effective than carboplatin-paclitaxel alone in both high-grade and non-high grade serous ovarian cancer.