Biomaterial Database

HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression. 2013

Wenna Chen, and Zheng Xiao, and Yachao Zhao, and Lina Huang, and Ganqin Du

Department of Neurology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

Suppression of hypoxia-inducible factor 1α (HIF-1α) has been shown to sensitize glioblastoma cells to temozolomide (TMZ) treatment via down-modulation of O6-methylguanine-DNA methyltransferase (MGMT) expression. To date, whether the efficacy of TMZ therapy is correlated with MGMT expression and whether HIF-1α suppression exerts similar effects in human pituitary adenoma cells have not been defined. In the present study, using an HIF-1α knockdown strategy and the HIF-1α inhibitor 2-methoxyestradiol (2ME), we demonstrated for the first time that HIF-1α suppression increases the efficacy of TMZ in human pituitary adenoma cells in vitro and in vivo. Our mechanistic study showed that HIF-1α suppression resulted in down-modulation of MGMT expression and decreased DNA damage repair ability as demonstrated by decreased RAD51 protein expression. These results suggest an HIF-1α-dependent regulation of MGMT expression in human pituitary adenoma cells, and HIF-1α knockdown or the HIF-1α inhibitor 2ME can confer TMZ sensitization in human pituitary adenomas. The clinical application of 2ME as an adjuvant therapy may be a potential approach to improve the efficacy of TMZ therapy for pituitary adenomas.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010911	Pituitary Neoplasms	Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.	Pituitary Cancer,Cancer of Pituitary,Cancer of the Pituitary,Pituitary Adenoma,Pituitary Carcinoma,Pituitary Tumors,Adenoma, Pituitary,Adenomas, Pituitary,Cancer, Pituitary,Cancers, Pituitary,Carcinoma, Pituitary,Carcinomas, Pituitary,Neoplasm, Pituitary,Neoplasms, Pituitary,Pituitary Adenomas,Pituitary Cancers,Pituitary Carcinomas,Pituitary Neoplasm,Pituitary Tumor,Tumor, Pituitary,Tumors, Pituitary
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003606	Dacarbazine	An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)	DTIC,5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide,Biocarbazine,DIC,DTIC-Dome,Decarbazine,Deticene,Dimethyl Imidazole Carboxamide,Dimethyl Triazeno Imidazole Carboxamide,ICDT,NSC-45388,Carboxamide, Dimethyl Imidazole,DTIC Dome,DTICDome,Imidazole Carboxamide, Dimethyl,NSC 45388,NSC45388
D004958	Estradiol	The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.	17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077204	Temozolomide	A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.	8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one,CCRG 81045,CCRG-81045,M&B 39831,M&B-39831,Methazolastone,NSC 362856,NSC-362856,TMZ-Bioshuttle,TMZA-HE,Temodal,Temodar,Temozolomide Hexyl Ester,CCRG81045,M&B39831,NSC362856,TMZ Bioshuttle
D000077584	2-Methoxyestradiol	A metabolite of estradiol that lacks estrogenic activity and inhibits TUBULIN polymerization. It has antineoplastic properties, including inhibition of angiogenesis and induction of APOPTOSIS.	(17 beta)-2-methoxyestra-1,3,5(10)-triene-3,17-diol,2-(methyl-11C)Methoxyestradiol,2-Methoxyestradiol, (17alpha)-isomer,2-Methoxyestradiol-17 beta,2-Methoxyoestradiol,Panzem,2 Methoxyestradiol,2 Methoxyestradiol 17 beta,2 Methoxyoestradiol
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia