title: Antiproliferative, antiinvasive, and proapoptotic activity of folate receptor α-targeted liposomal doxorubicin in nonfunctional pituitary adenoma cells.
abstract: There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)α is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FRα-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FRα and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9, and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FRα plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FRα.
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China. liuxiaohai09@yahoo.com.cn
authors: Xiaohai
authors: X
authors: Liu
authors: Sihai
authors: S
authors: Ma
authors: Congxin
authors: C
authors: Dai
authors: Feng
authors: F
authors: Cai
authors: Yong
authors: Y
authors: Yao
authors: Yakun
authors: Y
authors: Yang
authors: Ming
authors: M
authors: Feng
authors: Kan
authors: K
authors: Deng
authors: Guiling
authors: G
authors: Li
authors: Wenbing
authors: W
authors: Ma
authors: Bing
authors: B
authors: Xin
authors: Wei
authors: W
authors: Lian
authors: Guangya
authors: G
authors: Xiang
authors: Bo
authors: B
authors: Zhang
authors: Renzhi
authors: R
authors: Wang
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D058975:Folate Receptor 1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008081:Liposomes; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D058975:Folate Receptor 1; D008081:Liposomes; D009363:Neoplasm Proteins; D004317:Doxorubicin; D020169:Caspases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9