title: Effect of temozolomide on cell viability in gonadotroph adenoma cell lines.
abstract: Invasive pituitary adenomas are usually refractory to routine neurosurgery, radiosurgery or medications, and alternative therapies are needed. The effects of temozolomide (TMZ) on the inhibition of gonadotroph adenoma cell viability and hormone secretion were evaluated. Cell viability and IC50 values were evaluated after αT3-1 cells were treated with TMZ (31.25-1000 µM) or vehicle for 0-72 h. Cell cycle changes and the extent of apoptosis were detected using flow cytometry, TUNEL and TEM. The molecular mechanism of TMZ action was investigated by the Caspase-Glo® assay and immunoblotting. Gonadotropin secretion was assessed using an immunoassay system. TMZ dose- and time-dependently suppressed cell proliferation (P<0.01 vs. control, 250 µM, 24 h) and induced S-phase accumulation and G2/M-phase arrest (P<0.05 vs. control, 250 µM, 24 h). Early apoptotic cells increased following a 24-h TMZ incubation (P<0.001 vs. control, 250 µM), consistent with TEM and TUNEL detection that exhibited morphological features of apoptosis. TMZ (250 µM) increased the level of caspase-3/7 by 6-fold, caspase-9 by 7-fold and caspase-8 by 3-fold after a 24-h incubation, while it attenuated Bcl-2 expression (P<0.001 vs. control) and raised the proteolysis of PARP. Both FSH and LH levels were significantly decreased by TMZ (P<0.01 vs. control, 250 µM, 24 h). TMZ inhibited cell proliferation and hormone secretion, and induced cell cycle arrest and apoptotic cell death in gonadotroph adenoma cells via both death receptor and mitochondrial pathways, suggesting that it may represent a useful medical management strategy of invasive gonadotroph adenomas.
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China.
authors: Sihai
authors: S
authors: Ma
authors: Xiaohai
authors: X
authors: Liu
authors: Yong
authors: Y
authors: Yao
authors: Feng
authors: F
authors: Cai
authors: Congxin
authors: C
authors: Dai
authors: Xinjie
authors: X
authors: Bao
authors: Ming
authors: M
authors: Feng
authors: Junji
authors: J
authors: Wei
authors: Bo
authors: B
authors: Zhang
authors: Guilin
authors: G
authors: Li
authors: Wenbin
authors: W
authors: Ma
authors: Renzhi
authors: R
authors: Wang