title: HIF-1α Inhibition Sensitized Pituitary Adenoma Cells to Temozolomide by Regulating Presenilin 1 Expression and Autophagy.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Tangshan, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Kun
authors.affiliation: Department of Neurology, Tangshan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuling
authors.affiliation: Department of Neurosurgery, Tangshan, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Dongchun
authors.affiliation: Department of Neurology, Tangshan, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Bingbing
authors.affiliation: Department of Administration, Tangshan Worker Hospital, Tangshan, China tsgryylxl@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Xiaoli
authors.affiliation: Department of Neurosurgery, Hospital of Tangshan Iron and Steel Group Corporation, Tangshan, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Bin
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053764:Presenilin-1 / Q000378:metabolism*; D051381:Rats; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053764:Presenilin-1; D003606:Dacarbazine; D000077204:Temozolomide
keywords: HIF-1α; autophagy; lysosome acifidication; pituitary adenoma; presenilin 1; temozolomide