@Article{or.2026.085844,
AUTHOR = {Michal Kielbik, Izabela Szulc-Kielbik, Patrycja Przygodzka, Marek Nowak, Jacek Wilczyński, Magdalena Klink},
TITLE = {SNAIL 1 and SNAIL 2 in Chemoresistance and Invasive Potential of Ovarian Cancer–<i>In Vitro</i> and <i>Ex Vivo</i> Study},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/28269},
ISSN = {1555-3906},
ABSTRACT = {Objectives: Late diagnosis and the development of chemoresistance with metastatic potential are major limitations of effective treatment and long-term survival in epithelial ovarian cancer (EOC) patients. This study aimed to systematically compare the isoform-specific roles of SNAIL 1 and SNAIL 2 in the chemoresistance–invasiveness axis of ovarian cancer. Methods: We generated a cisplatin-resistant A2780<sub>CTP</sub> subline through stepwise cisplatin selection and used siRNA-mediated knockdown to evaluate the functional contribution of SNAIL 1 and SNAIL 2 in the resistant A2780<sub>CTP</sub> and inherently aggressive SK-OV-3 cell lines. These findings were extended by the analysis of clinically relevant models using 60 patient-derived samples (primary tumors and ascites) and 14 established primary ovarian cancer cell lines. Results: Stepwise cisplatin selection increased SNAIL 1 and SNAIL 2 expression, accompanied by enhanced resistance and metastatic traits. Knockdown of either isoform partially reversed cisplatin resistance and reduced migration/invasion, with isoform- and cell line-dependent differences. In patient-derived samples, SNAIL 1 and SNAIL 2 mRNA levels varied by anatomical site. Across primary cell lines, both isoforms positively correlated with cisplatin resistance, proliferation, and invasiveness, with SNAIL 1 frequently showing stronger associations. Conclusion: Our findings demonstrate that SNAIL 1 and SNAIL 2 contribute to adaptive responses to platinum therapy in ovarian cancer, linking them to chemoresistance and invasive behavior. While the isoforms exhibit partial non-redundancy, they are not fully interchangeable. These results support SNAIL transcription factors as relevant players in platinum-resistance and highlight the need for further mechanistic and <i>in vivo</i> studies to define isoform-specific therapeutic potential.},
DOI = {10.32604/or.2026.085844}
}