Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease

依西美坦通过下调 cAMP、pCREB 和 CD44 来阻止间皮瘤生长,为受此疾病影响的患者提供新的治疗选择

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作者:Barbara Nuvoli, Sabrina Germoni, Carlotta Morosetti, Raffaela Santoro, Giancarlo Cortese, Serena Masi, Iole Cordone, Rossella Galati

Background

Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models.

Conclusion

The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment.

Results

We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin.

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