Beschreibung:
<jats:p> 406 </jats:p><jats:p> Background: Gastric cancer is the third most common cause of cancer mortality worldwide, yet long-term survival in gastric cancer remains poor despite systemic therapeutic advances. FOLFOX (oxaliplatin, fluorouracil [5-FU], and leucovorin) is an approved chemotherapy regimen for gastric cancer treatment. Tumor Treating Fields (TTFields) are an antimitotic, loco-regional anticancer treatment delivered via non-invasive application of low intensity (1-3V/cm), intermediate frequency (100-500 kHz), alternating electrical fields. TTFields targets rapidly dividing cancer cells by disrupting microtubules leading to mitotic catastrophe, abnormal chromosome segregation, and apoptosis induction. We investigated the potential use of TTFields alone and in combination with FOLFOX for gastric carcinomas. Methods: Gastric cells (AGS and KATO III) were treated for 72 hours with TTFields (1.1 and 1.7 V/cm, respectively) at frequencies of 100-400 kHz using the inovitro system. Efficacy of TTFields and FOLFOX and its individual components was tested by applying TTFields at the optimal frequency in combination with various drug concentrations. Cell counts, apoptosis induction, clonogenic potential, and overall effect were determined. Results: The optimal TTFields frequency that led to the greatest cell count reduction (AGS, 55%; KATO III, 52%) was 150 kHz. The clonogenic potential was reduced by > 70% in both cell lines. TTFields combined with each FOLFOX component (oxaliplatin, 5-FU, or leucovorin) led to a significant reduction in AGS and KATO III cell survival (2-way ANOVA, P < 0.001 for each cell line) versus each treatment alone. In AGS, TTFields plus FOLFOX combination treatment led to a further reduction in the overall effect (cytotoxic and clonogenic; 79%) versus TTFields alone (65%) and FOLFOX alone (34%). Similar results were observed in KATO III cells. Conclusions: These results suggest that TTFields (150 kHz; optimal frequency) are an effective gastric cancer treatment; and combining TTFields with FOLFOX may further enhance efficacy. There is a strong rational to continue exploring the use of TTFields in combination with standard of care for gastric cancer treatment in the clinical settings. </jats:p>