Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin.
Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin.
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干扰素β对转钴胺素II受体表达和亚硝酰钴胺素抗肿瘤活性的影响。
DOI：
10.1093/jnci/94.13.1010
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Lindner,DanielJ
中科院分区：
文献类型：
--
作者：
Bauer,JosephA;Morrison,BeiH;Grane,RonaldW;Jacobs,BarbaraS;Dabney,Sally;Gamero,AnaM;Carnevale,KevinA;Smith,DanielJ;Drazba,Judith;Seetharam,Bellur;Lindner,DanielJ
背景：普遍存在的质膜转钴胺素II受体（TC II-R）介导钴胺素（Cbl;维生素B12），一种必需的微量营养素的摄取。肿瘤通常比正常组织需要更多的Cbl，并且增加的Cbl摄取可能是由于TC II-R表达增加。为了检查Cbl是否因此可以用作靶向化疗药物的载体分子，我们测试了Cbl的类似物，其具有一氧化氮作为配体，亚硝基钴胺素（NO-Cbl）。由于干扰素β（IFN-β）具有抗肿瘤作用并能增加某些膜受体的表达，我们研究了它是否能增强NO-Cbl的作用。在无胸腺裸鼠中建立人卵巢癌NIH-OVCAR-3细胞的异种移植瘤，并在单独和同时用NO-Cbl和IFN-β处理后监测肿瘤生长。在体外和体内检测TC Ⅱ-R表达和细胞凋亡。结果：NO-Cbl对肿瘤细胞的作用（ID 50为85-135 μM）明显强于正常细胞（ID 50为85-135 μM）（ID 50为2 μM）。NIH-OVCAR-3异种移植物的单一药剂NO-Cbl和IFN-β治疗诱导肿瘤消退，而组合治疗诱导肿瘤根除。IFN-β处理可增加TC Ⅱ-R的表达和[57 Co]钴胺素的摄取。与经NO-Cbl处理的NIH-OVCAR-3细胞相比，经NO-Cbl和IFN-β处理的NIH-OVCAR-3细胞更易发生凋亡，且多种凋亡相关基因的mRNA表达水平更高。结论：NO-Cbl通过激活外源性凋亡途径抑制肿瘤生长。IFN-β诱导TC Ⅱ-R表达增加，NO-Cbl增强其体外和体内抗肿瘤作用。
Background:The ubiquitous plasma membrane transcobalamin II receptor (TC II-R) mediates uptake of cobalamin (Cbl; vitamin B12), an essential micronutrient. Tumors often require more Cbl than normal tissue, and increased Cbl uptake may result from increased TC II-R expression. To examine whether Cbl could therefore be used as a carrier molecule to target a chemotherapy drug, we tested an analogue of Cbl with nitric oxide as a ligand, nitrosylcobalamin (NO-Cbl). Because interferon β (IFN-β) has antitumor effects and increases expression of some membrane receptors, we examined whether it may enhance the effects of NO-Cbl.Methods:Antiproliferative effects of NO-Cbl were assessed in 24 normal and cancer cell lines. Xenograft tumors of human ovarian cancer NIH-OVCAR-3 cells were established in athymic nude mice, and tumor growth was monitored after treatment with NO-Cbl and IFN-β, both individually and concomitantly. TC II-R expression and apoptosis was monitoredin vitroandin vivo. RNA protection assays and mitochondrial membrane potential assays were used to distinguish the extrinsic and intrinsic apoptotic pathways, respectively.Results:Cancer cell lines were more sensitive to NO-Cbl (with ID50s [the dose that inhibits growth by 50%] as low as 2 μM) than normal cell lines (with ID50s of 85–135 μM). Single-agent NO-Cbl and IFN-β treatment of NIH-OVCAR-3 xenografts induced tumor regression, whereas combination treatment induced tumor eradication. IFN-β treatment increased TC II-R expressionin vitroand uptake of [57Co]cobalaminin vivo. Compared with NIH-OVCAR-3 cells treated with NO-Cbl, cells treated with NO-Cbl and IFN-β were more apoptotic and expressed higher mRNA levels of various apoptosis-associated genes. No changes in mitochondrial membrane potential were observed in cells treated with NO-Cbl.Conclusion:NO-Cbl inhibited tumor growthin vivoby activating the extrinsic apoptotic pathway. The increased expression of TC II-R induced by IFN-β resulted in enhanced antitumor effects with NO-Cbl bothin vitroandin vivo.
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转钴胺 II 在人淋巴细胞蛋氨酸依赖性中的作用 1
DOI：
--
发表时间：
1988
期刊：
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
影响因子：
--
作者：
C. Hall;R. Chu;J. Begley
通讯作者：
J. Begley
线粒体介导一氧化氮诱导的细胞死亡
影响因子：
5.2
作者：
A. Bal;V. Borutaite;G. Brown
通讯作者：
G. Brown
钴胺素类似物在体外调节白血病细胞的生长。
影响因子：
11.2
作者：
G. Mclean;P. Pathare;D. Wilbur;A. Morgan;Clive S. Woodhouse;J. Schrader;H. Ziltener
通讯作者：
H. Ziltener
抗癌药物的输送。
影响因子：
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作者：
R. K. Zee;C. Cheng
通讯作者：
C. Cheng
转钴胺素 II 和白血病细胞的体外增殖。
影响因子：
2.6
作者：
G. Mclean;M. Williams;Clive S. Woodhouse;H. Ziltener
通讯作者：
H. Ziltener