Abstract B82: Application of modulated electro-hyperthermia for the cellular target therapy in ovarian cancer cells.

Background: Oncothermia as modulated electro-hyperthermia is an anti-cancer therapy that was approved by TUV-SUD in Germany, Health Canada in Canada, and Therapeutic Goods Administration in Australian. Oncothermia induces apoptosis via destroying the plasma membrane of cancer cells and leads to accumulation of heat-induced damages mostly in cells located in the tumor tissue while providing minimal damages to the surrounding normal tissue. Thus, oncothermia has recently become a potentially effective therapeutic tool for cancer. Methods: LabEHY-100, an oncothermia device from Oncotherm (Germany u0026 Hungary), was used for all in vitro studies. Ovarian cells were exposed to thermal damage induced by LabEHY-100, and subsequently, the cancer cells were analyzed in terms of viability, levels of apoptosis, autophagic markers and cell cycle status. In addition, xenograft tumors which generated by OVCAR-3 and patients derived tumor, were exposed to thermal damage induced by LabEHY-100 after which the tumor progression was monitored. The efficacy of combination therapy using both oncothermia and 3-methyladenine (3-MA), an autophagy inhibitor, was assessed using crystal violet assay. Results: Our studies showed that oncothermia resulted in growth inhibition in ovarian cancer cell tested. Apoptotic markers such as cleaved caspase-3 and PARP were upregulated in cells exposed to oncothermia compared to the control cells exposed to hyperthermia. Oncothermia also led to reduction in the mass and the volume of the tumors in the mouse transplanted with xenografts derived from cancer cells and ovarian cancer patient tumors. FACS analysis showed that cell cycles of these cells were not disrupted by oncothermia. Still there was a significant increase in the number of sub-G1 population, which consisted of dying cells including apoptotic cells. However, the xenograft cells recovered from cellular damage even after inducing autophagy via oncothermia. Combined treatment with oncothermia and 3-MA, a autophagy inhibitor, was more effective in inhibiting cancer cell growth than treatment with each alone. Conclusion: Oncothermia can potentially be an effective therapy for ovarian cancer cells. Conflict of interest : We obtained funding and in vitro device for electro-hyperthermia from HOSPICARE. Co., Ltd. (Seoul, Republic of Korea). Citation Format: Wookyeom Yang, Doo Byung Chay, Hanbyoul Cho, Sunghoon Kim, Jinkyoung Kong, Geumseon Son, Jihui Choi, Kim Jae-hoon. Application of modulated electro-hyperthermia for the cellular target therapy in ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B82.