2. Academic Validation
  3. Sulindac exhibits anti-proliferative and anti-invasive effects in uterine serous carcinoma cells

Sulindac exhibits anti-proliferative and anti-invasive effects in uterine serous carcinoma cells

  • J Cancer Res Clin Oncol. 2024 Aug 28;150(8):402. doi: 10.1007/s00432-024-05926-9.
Shuning Chen # 1 2,  Weimin Kong # 1,  Xiaochang Shen 1 2,  Boer Deng 1 2,  Jennifer Haag 2,  Nikita Sinha 2,  Catherine John 2,  Wenchuan Sun 2,  Chunxiao Zhou 3 4,  Victoria L Bae-Jump 5 6
Affiliations

Affiliations

  • 1 Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, People's Republic of China.
  • 2 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • 3 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. czhou@med.unc.edu.
  • 4 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. czhou@med.unc.edu.
  • 5 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. victoria_baejump@med.unc.edu.
  • 6 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. victoria_baejump@med.unc.edu.
  • # Contributed equally.
PMID: 39198302 DOI: 10.1007/s00432-024-05926-9
Abstract

Purpose: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial Cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells.

Methods: Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved Caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac.

Results: Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused Apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α.

Conclusion: Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.

Keywords

COX-2; Cell proliferation; Invasion; Sulindac; Uterine serous carcinoma.

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