Magnetic hyperthermia for induction of apoptosis of tumor xenograft with EGFR mutation

Abstract

Magnetic hyperthermia for induction of apoptosis of tumor xenograft with EGFR mutation Hasan Al Faruque, Eun-Sook Choi, Jung-Hee Kim, Eunjoo Kim Companion Diagnostics and Medical Technology Research Group, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea, 42988

Magnetic nanoparticles (MNPs) based hyperthermia (HT) treatment in solid tumor represents a promising approach to induce death of malignant cells either by apoptosis or necrosis through the heat generated by MNPs sub¬mitted to alternating magnetic fields. In this study, we investigate the effects of temperature distribution on the viability of cancer cells and the therapeutic potential in a xenograft model. An alternating magnetic field was applied to induce hyperthermia on the EGFR mutant lung cancer cell line (HCC827) and its xenograft model in Balb/C nu-nu mice. Moreover, TUNEL and western blot analysis was performed to measure the apoptosis induction potential in vivo after hyperthermia treatment. Tumor volume of the magnetic hyperthermia group stagnated in long term observation during 28 days, whereas the untreated control group showed liner tumor growth. TUNEL staining of tumor sections after magnetic hyperthermia treatment revealed distinct alteration of apoptotic cell number compares to no treated group. Immunoblot data also showed a significantly increased expression of BAX and cleaved caspase-9, which indicated that mitochondrial signaling pathway of apoptosis was involved in reducing the volume of the tumor. The animal showed no affection throughout the experiments, and we observed no pathological changes in hepatic and renal function test parameters. The intratumoral application of magnetic material was shown to be an efficient tool for the induction of hyperthermic temperature and kill the cancer cells both in vitro and in vivo conditions.