scholarly journals HIF-1α Inhibition Sensitized Pituitary Adenoma Cells to Temozolomide by Regulating Presenilin 1 Expression and Autophagy

2016 ◽  
Vol 15 (6) ◽  
pp. NP95-NP104 ◽  
Author(s):  
Zhang kun ◽  
Yang yuling ◽  
Wang dongchun ◽  
Xie bingbing ◽  
Li xiaoli ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Ph Value ◽  
Hypoxia Inducible Factor ◽  
Presenilin 1 ◽  
Gh3 Cells ◽  
Lysosomal Ph ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Effects ◽  
Autophagy Induction

Pituitary adenomas usually develop temozolomide resistance, which could compromise the anticancer effects of temozolomide. Suppression of hypoxia-inducible factor 1α has been shown to sensitize glioblastoma cells to temozolomide treatment according to previous reports. However, whether and how the suppression of hypoxia-inducible factor 1α could sensitize pituitary adenomas to temozolomide treatment are still poorly understood. In the present study, using hypoxia-inducible factor 1α knockdown strategy, we demonstrated for the first time that hypoxia-inducible factor 1α knockdown could inhibit temozolomide-induced autophagy in rat pituitary adenoma GH3 cells and thus increase antitumor efficacy of temozolomide. Furthermore, we found hypoxia-inducible factor 1α knockdown could block autophagy process through neutralizing lysosomal pH value but not inhibiting autophagy induction. Finally, we found hypoxia-inducible factor 1α could regulate lysosomal pH value through regulating full length presenilin 1 expression, and exogenous reexpression of presenilin 1could restore lysosome acidic levels. Our data indicated hypoxia-inducible factor 1α knockdown could be a potential approach to improve the efficacy of temozolomide therapy for pituitary adenomas.

Expression of Hypoxia-Inducible Factor 1α and Cathepsin D in Pituitary Adenomas

2005 ◽  
Vol 16 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Daizo Yoshida ◽  
Kyongsong Kim ◽  
Michio Yamazaki ◽  
Akira Teramoto
Keyword(s):  
Pituitary Adenomas ◽  
Cathepsin D ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α

Temozolomide-induced inhibition of pituitary adenoma cells

2011 ◽  
Vol 114 (2) ◽  
pp. 354-358 ◽  
Author(s):  
Jason Sheehan ◽  
Jessica Rainey ◽  
James Nguyen ◽  
Ruthie Grimsdale ◽  
Shaojie Han
Keyword(s):  
Cell Proliferation ◽  
Pituitary Adenoma ◽  
Cell Lines ◽  
Pituitary Adenomas ◽  
Apoptotic Cell ◽  
Multimodality Treatment ◽  
Prolactin Secretion ◽  
Significant Inhibition ◽  
Gh3 Cells ◽  
Tunel Staining

Object Aggressive pituitary adenomas frequently require multimodality treatment including pituitary-suppressive medications, microsurgery, and radiation therapy or radiosurgery. The effectiveness of temozolomide in terms of growth suppression and decreased hormonal production is evaluated. Methods Three pituitary adenoma cell lines—MMQ, GH3, and AtT20—were used. A dose escalation of temozolomide was performed for each cell line, and inhibition of cell proliferation was assessed using an MTT assay. Concentrations of temozolomide that produced statistically significant inhibition of cell proliferation for each cell type were identified. Extent of apoptosis for each selected temozolomide concentration was studied using TUNEL staining. The effect of temozolomide on prolactin secretion in MMQ and GH3 cells was also measured via ELISA. Results Significant inhibition of cell proliferation was noted for MMQ and GH3 cells at a concentration of 250 μM temozolomide. The AtT20 cells demonstrated statistically significant cell inhibition at a concentration of only 50 μM temozolomide (p < 0.05). Apoptosis significantly increased in all cell lines in as little as 24 hours of incubation at the respective temozolomide concentrations (p < 0.05). Prolactin secretion in the prolactin secreting MMQ and GH3 cell lines was inhibited by 250 μM temozolomide. Conclusions Temozolomide inhibits cell proliferation and induces apoptotic cell death in aggressive pituitary adenoma cells. A reduction in hormonal secretion in prolactinoma cells was also afforded by temozolomide. Temozolomide may prove useful in the multimodality management of aggressive pituitary adenomas.

scholarly journals Effects of low-dose ionising radiation on pituitary adenoma: is there a role for L-type calcium channel?

2005 ◽  
Vol 48 (spe2) ◽  
pp. 185-190
Author(s):  
Marcella Araugio Soares ◽  
Raquel Gouvêa dos Santos
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Low Dose ◽  
Calcium Influx ◽  
Calcium Currents ◽  
Gh3 Cells ◽  
Live Cells ◽  
Radiation Induced ◽  
Induced Apoptosis

Pituitary adenomas constitute about 6-18% of brain tumours in adults. Activation of voltage gated calcium currents can account for growth hormone oversecretion in some GH-secreting pituitary adenomas that produce an acromegaly appearance and increase mortality. Ca2+ ions, as mediators of intracellular signalling, are crucial for the development of apoptosis. However, the role of [Ca2+] in the development of apoptosis is ambiguous. In this study, the effects of low-dose ionising gamma radiation (60Co) on rat pituitary adenoma cells survival and proliferation and the role of calcium channels on the apoptosis radio-induced were evaluated. Doses as low as 3 Gy were found to inhibit GH3 cell proliferation. Even though there was a significant number of live cells,168 hours following irradiation, they were not able to proliferate. The results indicate that the blockade of extracellular calcium influx through these channels does not interfere in the radiation-induced apoptosis in GH3 cells.

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