Evaluation of the molecular therapeutic effect of dienogest in endometriosis in experimental rat model

PURPOSE: 'Dienogest' is a progestagenic agent which is known to have therapeutic effect on endometriosis. The aim of this study is evaluation of this therapeutic effect in a molecular basis. MATERIALS AND METHODS: This study was performed in Medical Biology Department of Celal Bayar University Institute of Medical Sciences and Animal Investigations Laboratory of Manisa Celal Bayar University. Poetntial molecular pathways of 'dienogest' was investigated by Western blot and PCR analyses in rat endometriosis model. The collected data were statistically analyzed using GraphPad Prism (version 9) ANOVA test. P value<0.05 was accepted as statistically significant. RESULTS: PCR analysis showed upregulated genetic expressions of caspase 12, Bax, p38, AKT, c-MYC and BCL2L1 and downregulated genetic expressions of caspase-3, caspase-6, Bad, BCL2A1, TRADD, TRAF1-2, Bid and p53 in the dienogest group. Genetic expressions of caspase-3, caspase-12, Bad and AKT were found to be significantly higher (p<0.005) in progesterone group compared to control group. Dienogest compared to natural progesterone showed stronger activity on phospho-ERK and phospho-p38 pathways, similar activity on ERK and b-Actin signaling pathways, and weaker activity on PERK, SAPK/JNK and phospho-46 pathways based on Western-blot analysis. CONCLUSION: The use of alternative cellular pathways by dienogest compared to natural progesterone may partially explain the therapeutic success of dienogest. In conclusion, dienogest is a hormone, acting via anti-inflammatory, pro-apoptotic and endoplasmic reticulum stress pathways at the endometriotic cellular level and can be considered a successful alternative therapeutic option.