Effects of glivec combined with everolimus on mouse pituitary AtT-20 cells / 医学研究生学报

ABSTRACT

Objective Medication for pituitary adenomas is mainly targeted on the prolactin-secreting and growth-hormone types and shows poor therapeutic effects on other adenomas .Therefore, new drugs urgently need to be developed for this purpose .This study was to investigate the effects of glivec and everolimus on mouse pituitary AtT-20 cells and their molecular mechanisms in vitro. Methods Mouse pituitary AtT-20 cells were incubated with glivec or everolimus or combination of both and their inhibitory effect on the proliferation of the cells was measured by CCK-8 assay.The mRNA levels of AKT and ERK were determined by q-PCR and the ex-pressions of the phosphorylated AKT (p-AKT) and ERK (p-ERK) were detected by Western blot. Results Used alone, both glivec and everolimus inhibited the proliferation of the AtT-20 cells in a time-and dose-dependent manner , but their combination produced a mutually antagonistic effect, with combination index values of 1.13 ±0.06, 1.12 ±0.03, and 1.07 ±0.03 respectively.The two a-gents , either used alone or in combination , induced no significantly inhibitory effects on the mRNA and protein expressions of AKT and ERK ( P >0.05 ).Both glivec and everolimus up-regulated the expressions of p-AKT and p-ERK, and their combination manifested an even stronger effect (P>0.05). Conclusion Both glivec and everolimus inhibit the proliferation of AtT-20 cells when administered alone, but their combination produces an antagonistic effect .Their action mechanism might be that when targeting some signaling path-ways to inhibit cell proliferation , glivec, as well as everolimus , in-duces a feedback activation of AKT and ERK .