Early Changes in mRNA and Protein Expression Related to Cancer Treatment by Modulated Electrohyperthermia

Abstract

Modulated electrohyperthermia (mEHT), generated by capacitive coupled, modulated 13.56 MHz radiofrequency, is a noninvasive technique for targeted tumor treatment based on elevated ion concentration and electric admittance in malignant tumors. In this study, we tested early changes in protein expression related to tumor destruction upon a single shot of 30-minute mEHT treatment of xenografted human colorectal cell line (HT29) implanted into the femoral region of Balb/c nu/nu mice. Treatment-related mRNA expression profiling was done using the human genome U133 Plus 2.0 Arrays. Apoptosis protein arrays and immunohistochemistry were performed for validating changes at the protein level. The mEHT treatment resulted in major expression changes in 48 genes including several heat-shock proteins. Apoptosis protein arrays revealed the upregulation of death receptors, Bcl-2 superfamily mitochondrial apoptosis regulatory proteins, and heat-shock proteins, which were also confirmed in situ. Within 24-hour post-treatment, mEHT resulted in the upregulation apoptosis induction and heat-shock-related gene and protein expression in HT29 colorectal cancer xenografts contributing to tumor destruction.