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Background: Gastric cancer, one of the most common types of cancers, is mainly treated with the FOLFOX chemotherapy regimen (oxaliplatin, fluorouracil [5-FU], and leucovorin); yet long-term survival remains poor. Tumor Treating Fields (TTFields) are electrical fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cell death. In several tumor types, the mechanism of action of TTFields included an antimitotic effect and DNA damage induction with impaired DNA damage repair. The current study aimed to examine the efficacy of TTFields for treating gastric cancer cells, and the potential application of TTFields concomitant with FOLFOX. Methods: Human gastric cancer cell lines, AGS and KATO III, were treated with TTFields (intensity of 1.1 and 1.7 V/cm, respectively; frequency of 150 kHz) using the inovitro system. Cell count and colony formation were examined following treatment, and the overall effect calculated by multiplication of the two. RNA sequencing was also performed on samples from control and TTFields-treated cells. Mitotic spindle defects, chromosome miss-localization, and DNA double strand breaks (DSB) formation were examined by fluorescent staining for α-tubulin, phospho-histone 3 (PH3), and phospho-histone H2AX (γH2AX), respectively. Expression of DNA repair proteins was measured using Western Blot. The impact of TTFields with FOLFOX and its individual therapeutic components, oxaliplatin and 5-FU on cell count and clonogenicity was tested. Results: TTFields reduced cell count and the colony forming ability of the cells. Cells treated with TTFields displayed abnormal mitotic figures and increased levels of DNA damage. Expression of DNA repair proteins was downregulated following treatment with TTFields, as evident from RNA and protein levels. Furthermore, TTFields augmented the cytotoxic and clonogenic effects of FOLFOX and its individual therapeutic components, oxaliplatin and 5-FU. Conclusions: TTFields show potential as an effective gastric cancer treatment, with a mechanism of action involving an anti-mitotic effect and DNA damage repair impairment. TTFields may be applied to enhance the efficacy of gastric cancer standard-of-care. Citation Format: Naama Flint-Brodsly, Einav Zeevi, Kerem Wainer-Katsir, Hila Fishman, Antonia Martinez-Conde, Eyal Dor-On, Mijal Munster, Yaara Porat, Tali Voloshin, Shiri Davidi, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Treatment of gastric cancer cells with tumor treating fields (TTFields) and concomitant FOLFOX [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2723. |
