PhD Scientific Days 2023

Translational Medicine I.

Non-steroid anti-inflammatory treatment enhances the efficacy of modulated electro hyperthermia on triple negative breast cancer and melanoma cancer models in vivo.

Text of the abstract

Introduction: Modulated electro-hyperthermia (mEHT) is an advanced option in the hyperthermia field, applying a 13.56 MHz radiofrequency electromagnetic current to induce tumor-specific damage. This study investigates the mEHT-induced molecular effect and the potential of combination non-steroid anti-inflammatory drugs (NSAIDs) to enhance its anti-tumor effects in 4T1 triple-negative breast cancer (TNBC) and B16F10 melanoma mouse models.
Materials and methods: 4T1 TNBC and B16F10 melanoma cell lines were injected into Balb/C and C57BL/6 mice, respectively. They have been treated according to the protocol with only mEHT or mEHT combined with non-selective COX-inhibitors (Aspirin) or selective COX2 inhibitors (SC236). Tumor volume was monitored by ultrasound and a digital caliper. At the end of the experiments, mice were euthanized and tumors excised for molecular studies.
Results and discussion: Here we report that mEHT monotherapy stimulates local IL1-beta and IL6, and consequently cyclooxygenase 2 (COX 2) production. These effects could be considered as part of a self-defensive, wound-healing reaction of the tumor to protect itself from the mEHT-induced stress. In the present study, we combined mEHT with non-steroid anti-inflammatory drugs (NSAIDs), the non-selective (Aspirin), or the selective COX2 inhibitor (SC236) in vivo. All of these therapies have already demonstrated antitumor effects in various cancer models as monotherapies. Here we demonstrate that NSAID treatment synergistically increased the effect of mEHT in 4T1 TNBC. Tumor weight and tumor volume (measured by ultrasound and a digital caliper) were lowest, and the tumor destruction ratio (TDR) was the highest in the combination treated (NSAID + mEHT) groups. Tumor damage was accompanied by a significant increase in cleaved caspase-3 (cC3), suggesting an important role for apoptosis. Similarly, in the B16F10 melanoma model, lungs nodules were significantly less in mice treated with mEHT + Aspirin.
Conclusion: NSAIDs effectively enhance the mEHT anti-tumor effect in TNBC and melanoma cancer models; they increase tumor destruction, where apoptosis may play a role. Disecting the exact molecular mechanisms further is under our current investigation.

First author: Nino Giunashvili
nino.giunashvili@phd.semmelweis.hu
Supervisor: Peter Hamar
Funding: SE250+ scholarship EFOP-3.6.3-VEKOP-16-2017-00009