Cytostatic and Non-Apoptotic Effects of Vinorelbine-Based Therapy in 3D Endometrial Cancer Spheroids

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.