OBJECTIVE
Endometriosis is characterized by the ectopic growth of endometrial tissue, linked to disrupted proliferation and apoptosis. c-Abl (Abelson tyrosine kinase), implicated in these processes, is inhibited by imatinib. However, its role in endometriosis remains unclear. We hypothesized that imatinib may be used as a therapeutic target for endometriosis.
MATERIALS AND METHODS
Endometriotic tissues were collected from patients (n=6, aged 23-45) at Yeditepe University Hospital. Stromal cells were cultured in DMEM/F12 (10% FBS), then treated with 0 (control), 12.5, 25, and 50 µM imatinib for 48 and 72 hours. Proliferation was measured with an automatic cell counter. Apoptosis/viability was assessed via Annexin V/PI staining, and the cell cycle by DNA content analysis. Migration was evaluated by a wound-healing assay. c-Abl and phospho-c-Abl (p-c-Abl) levels were assessed by immunofluorescence.
RESULTS
Proliferation of endometriotic cells significantly decreased at 48 hours with 25 µM and 50 µM imatinib, and at 72 hours in all treatment groups (p<0.01). Early apoptosis was increased in all treatment groups (p<0.05), while late apoptosis was elevated in the 25 µM and 50 µM (p<0.05). Necrotic population was increased in the 12.5 µM and 25 µM groups at 48 hours (p<0.05), and in the 50 µM group at 72 hours (p<0.05). Cell cycle analysis at 48 hours showed G0/G1 arrest with 12.5 μM imatinib (p<0.001), while 50 μM caused cell cycle arrest in S (p<0.05) and G2/M phases (p<0.0001) and promoted aneuploidy. In 72 hours, 12.5 μM imatinib led to G0/G1 arrest (p<0.05), and aneuploidy was observed at 25 and 50 µM imatinib, but cell cycle arrest occurred only at 50 µM, with G2/M arrest (p<0.0001). Cell migration is decreased in all treatment groups(p<0.001). Immunofluorescence in 72 hours showed increased c-Abl at 50µM (p<0.05). In contrast, p-c-Abl levels decreased in all treatment groups (p<0.05).
CONCLUSIONS
Imatinib inhibited proliferation and migration while promoting apoptosis and necrosis in a dose- and time-dependent manner. It alters the cell cycle by causing arrest and may induce aneuploidy. These findings suggest that inhibition of c-Abl activity may play a significant role in endometriotic cell behavior.
IMPACT STATEMENT
The expanding understanding of c-Abl inhibition in endometriosis could provide valuable insights into the underlying mechanisms of endometriosis. We believe that our results may guide future studies on endometriosis and contribute to the development of new therapeutic approaches.
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