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ARTICLE

SNAIL 1 and SNAIL 2 in Chemoresistance and Invasive Potential of Ovarian Cancer–In Vitro and Ex Vivo Study

Michal Kielbik1,*, Izabela Szulc-Kielbik1, Patrycja Przygodzka1, Marek Nowak2,3, Jacek Wilczyński4, Magdalena Klink1,*
1 Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland
2 Department of Operative Gynecology and Gynecologic Oncology, Polish Mother’s Memorial Hospital–Research Institute, Lodz, Poland
3 Department of Operative and Endoscopic Gynecology, Medical University of Lodz, Lodz, Poland
4 Department of Surgical and Oncological Gynecology, Medical University of Lodz, Lodz, Poland
* Corresponding Author: Michal Kielbik. Email: email; Magdalena Klink. Email: email

Oncology Research https://doi.org/10.32604/or.2026.085844

Received 19 May 2026; Accepted 03 August 2026; Published online 10 September 2026

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 A2780CTP subline through stepwise cisplatin selection and used siRNA-mediated knockdown to evaluate the functional contribution of SNAIL 1 and SNAIL 2 in the resistant A2780CTP 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 in vivo studies to define isoform-specific therapeutic potential.

Keywords

Epithelial ovarian cancer; SNAIL transcription factors; chemoresistance; invasiveness

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