Cytostatic and Non-Apoptotic Effects of Vinorelbine-Based Therapy in 3D Endometrial Cancer Spheroids
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Department of Histology and Embryology, Faculty of Medicine, İstanbul Atlas University, 34403 İstanbul, Turkey
2
Department of Obstetrics and Gynecology, Faculty of Medicine, İstanbul Atlas University, 34403 İstanbul, Turkey
*
Author to whom correspondence should be addressed.
Biology 2026, 15(7), 576; https://doi.org/10.3390/biology15070576
Submission received: 10 March 2026
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Revised: 24 March 2026
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Accepted: 30 March 2026
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Published: 3 April 2026
(This article belongs to the Section Cancer Biology)
Simple Summary
Endometrial cancer is one of the most common gynecological cancers, and treatment can be challenging when tumor cells become resistant to therapies that rely on apoptosis (programmed cell death). In this study, we used a three-dimensional tumor model to better mimic real tumor behavior and investigated the effects of vinorelbine, alone or combined with lithium chloride or medroxyprogesterone acetate. We found that these treatments significantly reduced tumor cell proliferation without strongly inducing cell death. Instead, the drugs appeared to slow down or stop tumor growth by suppressing DNA synthesis and altering cell cycle progression. These findings suggest that some anticancer therapies may control tumor growth without necessarily killing the cells, which could be particularly useful in apoptosis-resistant cancers. This approach may help guide the development of alternative treatment strategies for patients with advanced or recurrent endometrial cancer.
Abstract
Resistance to apoptosis represents a major therapeutic challenge in advanced and recurrent endometrial cancer. This study investigated whether vinorelbine, alone or in combination with lithium chloride (LiCl) or medroxyprogesterone acetate (MPA), suppresses tumor growth through non-apoptotic mechanisms in a three-dimensional spheroid model of Ishikawa endometrial cancer cells. Proliferation was assessed by BrdU incorporation, cell cycle distribution by flow cytometry, and apoptosis by Annexin V/propidium iodide staining. Vinorelbine-based treatments significantly reduced DNA synthesis and were associated with decreased S-phase fractions and altered cell cycle distribution. These effects were sustained over time and were more pronounced in combination treatments. Importantly, no consistent increase in apoptotic cell death was observed, and most cells remained viable despite strong suppression of proliferation. These findings indicate that vinorelbine-based regimens inhibit tumor spheroid growth predominantly through cytostatic mechanisms rather than induction of apoptosis. This non-apoptotic growth-control strategy may be relevant for the management of apoptosis-resistant endometrial cancer.
