ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1520771
Sulindac exhibits anti-proliferative and anti-invasive effects and enhances the sensitivity to paclitaxel in ovarian cancer
Provisionally accepted
Shuning Chen1
Weimin Kong2
Xiaochang Shen1
Nikita Sinha1Jennifer Haag1Boer Deng2Haomeng Zhang1Catherine John1Wenchuan Sun1
Chunxiao Zhou1*
Victoria Bae-Jump1- 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, United States
- 2Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
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Chronic inflammation is a key contributor to carcinogenesis, progression, and chemoresistance in ovarian cancer (OC), making inflammatory pathways a logical therapeutic target for the treatment of this disease.Sulindac, a commonly used non-steroidal anti-inflammatory drug, has demonstrated anti-proliferative and anti-invasive effects on several preclinical models of cancer. Little is known about the biological effects of sulindac on cell growth and invasion in OC. In this study, we investigated the antitumorigenic effects of sulindac in human OC cell lines and a transgenic mouse model of OC (KpB). Our results demonstrated that sulindac significantly inhibited cell proliferation, induced cellular stress and apoptosis, caused G1 phase cell cycle arrest, and reduced cell invasion, and suppressed Cox-2 and NF-κB pathways in the MES and OVCAR5 cell lines. Inhibition of cellular stress by N-acetylcysteine partially reversed the anti-proliferative and antiinvasive effects of sulindac. The combination of sulindac and paclitaxel produced synergistic effects in inhibiting cell growth in both paclitaxel sensitive and resistant MES cells. Treatment with sulindac for 4 weeks effectively reduced tumor growth, improved serum levels of inflammatory cytokines and chemokines, and reduced the expression of Cox-2 of ovarian tumors in KpB mice compared with untreated mice. These findings provide support for the development of clinical trials repurposing sulindac in the treatment of OC, possibly in combination with paclitaxel.
Keywords: ovarian cancer, Sulindac, Cell Proliferation, invasion, Synergy, Paclitaxel
Received: 01 Nov 2024; Accepted: 18 Apr 2025.
Copyright: © 2025 Chen, Kong, Shen, Sinha, Haag, Deng, Zhang, John, Sun, Zhou and Bae-Jump. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chunxiao Zhou, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, United States
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