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Cancer research:避孕药与降胆固醇药物联用可治血癌

来源:生物谷 2015-05-18 10:43

                                                                 

2015年5月18日讯 /生物谷BIOON/ --近日,一项研究表明降胆固醇药物--苯扎贝特和具有避孕作用的类固醇药物--醋酸甲羟孕酮联合使用可有效治疗癌症,并且没有发现明显的毒副作用。国际学术期刊cancer research发表了英国伯明翰大学研究人员的这一最新发现。
 
在一些初步临床实验中,研究人员对患有急性髓系白血病的老年病人进行了苯扎贝特和醋酸甲羟孕酮的联合治疗,病人的平均生存时间比进行标准姑息疗法的病人长3个月,除此之外,这种联合治疗药物与化疗药物并用还可有效治疗患有伯基特淋巴瘤的儿童。但在该文章发表之前,这种治疗方法是否通过相同机制治疗两种不同的血液癌症一直未有研究。
 
在该项研究中,研究人员发现这种联合用药的方法能够在两种不同的癌细胞类型中阻断同一个参与脂肪酸合成的关键酶,而脂肪酸是促进癌细胞生长的重要营养物质。他们还证明药物联合治疗能够使这个关键酶--硬脂酰辅酶A去饱和酶发生失活,从而促进癌细胞死亡。
 
这一发现为治疗同样依赖硬脂酰辅酶A去饱和酶的其它类型癌症,如慢性淋巴细胞白血病,部分类型的非霍奇金淋巴瘤,前列腺癌,结肠癌以及食管癌开辟了新的方向。研究人员还希望在骨髓增生异常综合征病人身上进行该联合药物治疗的进一步临床验证。这项研究对于癌症治疗以及癌症治疗药物应用具有非常重要的启示。(生物谷Bioon.com)
 
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Drug redeployment to kill leukaemia and lymphoma cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids
 
Andrew D Southam1,*, Farhat L Khanim2, Rachel E Hayden2, Julia K Constantinou1, Katarzyna Koczula3, Robert H Michell1, Mark R Viant2, Mark T Drayson4, and Chris M Bunce2
 
The redeployed drug combination of bezafibrate and medroxyprogesterone acetate (designated BaP) has potent in vivo anticancer activity in acute myeloid leukemia (AML) and endemic-Burkitt's lymphoma (eBL) patients; however its mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis is a hallmark of many cancers and that these drugs can affect lipid metabolism, we hypothesized that BaP exerts anticancer effects by disrupting lipogenesis. We applied mass spectrometry-based lipidomics and gene and protein expression measurements of key lipogenic enzymes [acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1)] to AML and eBL cell lines treated with BaP. BaP treatment decreased fatty acid and phospholipid biosynthesis from glucose. The proportion of phospholipid species with saturated and monounsaturated acyl chains were also decreased after treatment, while those with polyunsaturated chains increased. BaP decreased SCD1 protein levels in each cell line (0.46 - 0.62-fold, p<0.023) and decreased FASN protein levels across all cell lines (0.87-fold decrease, p=1.7×10-4). Changes to ACC1 protein levels were mostly insignificant. Supplementation with the SCD1 enzymatic product, oleate, rescued AML and e-BL cells from BaP cell killing and decreased levels of BaP-induced reactive oxygen species whereas supplementation with the SCD1 substrate (and FASN product), palmitate, did not rescue cells. In conclusion, these data suggest that the critical anticancer actions of BaP are decreases in SCD1 levels and monounsaturated fatty acid synthesis. To our knowledge, this is the first time that clinically available anti-leukemic and anti-lymphoma drugs targeting SCD1 have been reported.
 
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