Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions

다국어 초록 (Multilingual Abstract)

Telmisartan suppresses the development of endometriotic lesions. However, the drug also up‐regulates the expression of COX‐2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX‐2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone.
Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were treated daily with an i.p. injection of telmisartan (10 mg·kg−1), parecoxib (5 mg·kg−1), a combination of telmisartan and parecoxib or vehicle. Therapeutic effects on lesion survival, growth, vascularization, innervation and protein expression were studied over 4 weeks by high‐resolution ultrasound imaging as well as immunohistochemical and Western blot analyses.
Telmisartan‐treated lesions exhibited a significantly reduced lesion volume when compared with vehicle‐treated controls and parecoxib‐treated lesions. This inhibitory effect of telmisartan was even more pronounced when it was used in combination with parecoxib. The combination therapy resulted in a reduced microvessel density as well as lower numbers of proliferating Ki67‐positive cells and higher numbers of apoptotic cleaved caspase‐3‐positive stromal cells within the lesions. This was associated with a lower expression of COX‐2, MMP‐9 and p‐Akt/Akt when compared with controls. The application of the two drugs further inhibited the ingrowth of nerve fibres into the lesions.
Combination therapy with telmisartan and a COX‐2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis.