title: CRM1 as a new therapeutic target for non-Hodgkin lymphoma.
abstract: The chromosomal region maintenance 1 (CRM1) may serve as a novel target for cancer treatment. Here, we investigated the anti non-Hodgkin lymphoma (NHL) activity of two novel CRM1 inhibitors (KPT-185 and KPT-276) in vitro and in vivo. KPT-185 displayed potent antiproliferative properties and induced cell-cycle arrest and apoptosis in several NHL cell lines and patients' tumor cells. The antitumor activity mainly consisted of inducing caspase cleavage and downregulating the expression of antiapoptotic proteins such as CRM1, nuclear factor-κB, and survivin. Furthermore, oral administration of KPT-276 significantly suppressed tumor growth in mice with Jeko-1 xenograft without any major toxic effects.
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Yinchen
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China. Electronic address: syuankaipumc@126.com.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000178:Acrylamides / Q000494:pharmacology*; D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D028884:Karyopherins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000097606:Exportin 1 Protein
chemical_list: D000178:Acrylamides; D000179:Acrylates; D000970:Antineoplastic Agents; D020169:Caspases; D028884:Karyopherins; D009363:Neoplasm Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014230:Triazoles; D000097606:Exportin 1 Protein; C576639:KPT-185; C586831:KPT-276
keywords: CRM1; CRM1 inhibitor; Non-Hodgkin lymphoma