期刊
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
卷 15, 期 6, 页码 NP95-NP104出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1533034615618834
关键词
HIF-1 alpha; pituitary adenoma; autophagy; temozolomide; lysosome acifidication; presenilin 1
类别
Pituitary adenomas usually develop temozolomide resistance, which could compromise the anticancer effects of temozolomide. Suppression of hypoxia-inducible factor 1 alpha has been shown to sensitize glioblastoma cells to temozolomide treatment according to previous reports. However, whether and how the suppression of hypoxia-inducible factor 1 alpha could sensitize pituitary adenomas to temozolomide treatment are still poorly understood. In the present study, using hypoxia-inducible factor 1 alpha knockdown strategy, we demonstrated for the first time that hypoxia-inducible factor 1 alpha 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 1 alpha knockdown could block autophagy process through neutralizing lysosomal pH value but not inhibiting autophagy induction. Finally, we found hypoxia-inducible factor 1 alpha could regulate lysosomal pH value through regulating full length presenilin I expression, and exogenous reexpression of presenilin I could restore lysosome acidic levels. Our data indicated hypoxia-inducible factor 1 alpha knockdown could be a potential approach to improve the efficacy of temozolomide therapy for pituitary adenomas.
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