TY  - EJOU
AU  - Kielbik, Michal 
AU  - Szulc-Kielbik, Izabela 
AU  - Przygodzka, Patrycja 
AU  - Nowak, Marek 
AU  - Wilczyński, Jacek 
AU  - Klink, Magdalena 

TI  - SNAIL 1 and SNAIL 2 in Chemoresistance and Invasive Potential of Ovarian Cancer–<i>In Vitro</i> and <i>Ex Vivo</i> Study
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - 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.
KW  - Epithelial ovarian cancer; SNAIL transcription factors; chemoresistance; invasiveness

DO  - 10.32604/or.2026.085844