Objective Pituitary adrenocorticotropic hormone(ACTH)-secreting adenoma is a relatively intractable endocrine adenoma that can cause a range of severe metabolic disorders and pathological changes involving multiple sy...Objective Pituitary adrenocorticotropic hormone(ACTH)-secreting adenoma is a relatively intractable endocrine adenoma that can cause a range of severe metabolic disorders and pathological changes involving multiple systems.Previous studies have shown that celastrol has antitumor effects on a variety of tumor cells via the AKT/mTOR signaling.However,whether celastrol has pronounced antitumor effects on pituitary ACTH-secreting adenoma is unclear.This study aimed to identify a new effective therapeutic drug for pituitary ACTH-secreting adenoma.Methods Mouse pituitary ACTH-secreting adenoma cells(AtT20 cells)were used as an experimental model in vitro and to establish a xenograft tumor model in mice.Cells and animals were administered doses of celastrol at various levels.The effects of celastrol on cell viability,migration,apoptosis and autophagy were then examined.Finally,the potential involvement of AKT/mTOR signaling in celastrol’s mechanism was assessed.Results Celastrol inhibited the proliferation and migration of pituitary adenoma cells in a time-and concentration-dependent manner.It blocked AtT20 cells in the G0/G1 phase,and induced apoptosis and autophagy by downregulating the AKT/mTOR signaling pathway.Similar results were obtained in mice.Conclusion Celastrol exerts potent antitumor effects on ACTH-secreting adenoma by downregulating the AKT/mTOR signaling in vitro and in vivo.展开更多
基金This work was supported by the National Natural Science Youth Foundation of China(No.81602204).
文摘Objective Pituitary adrenocorticotropic hormone(ACTH)-secreting adenoma is a relatively intractable endocrine adenoma that can cause a range of severe metabolic disorders and pathological changes involving multiple systems.Previous studies have shown that celastrol has antitumor effects on a variety of tumor cells via the AKT/mTOR signaling.However,whether celastrol has pronounced antitumor effects on pituitary ACTH-secreting adenoma is unclear.This study aimed to identify a new effective therapeutic drug for pituitary ACTH-secreting adenoma.Methods Mouse pituitary ACTH-secreting adenoma cells(AtT20 cells)were used as an experimental model in vitro and to establish a xenograft tumor model in mice.Cells and animals were administered doses of celastrol at various levels.The effects of celastrol on cell viability,migration,apoptosis and autophagy were then examined.Finally,the potential involvement of AKT/mTOR signaling in celastrol’s mechanism was assessed.Results Celastrol inhibited the proliferation and migration of pituitary adenoma cells in a time-and concentration-dependent manner.It blocked AtT20 cells in the G0/G1 phase,and induced apoptosis and autophagy by downregulating the AKT/mTOR signaling pathway.Similar results were obtained in mice.Conclusion Celastrol exerts potent antitumor effects on ACTH-secreting adenoma by downregulating the AKT/mTOR signaling in vitro and in vivo.
