替莫唑胺通过线粒体途径诱导人黑素瘤细胞凋亡研究  

Temozolomide induces apoptosis through mitochondrial pathway in human melanoma cells

作　　者：王红梅[1] 蒋爱军[2] 韩正祥[1] 蒋冠[3] 

机构地区：[1]徐州医学院附属医院肿瘤科,江苏徐州221002 [2]徐州医学院附属医院立体定向科 [3]徐州医学院附属医院皮肤科

出　　处：《徐州医学院学报》2015年第10期678-680,共3页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金（81372916）

摘　　要：目的：研究替莫唑胺（ temozolomide， TMZ）诱导黑素瘤细胞A375、MV3、M14凋亡的机制。方法将对数生长期的黑素瘤细胞A375、MV3、M14分别用TMZ干预。应用CCK－8法检测黑素瘤细胞抑制率，应用Western blot法检测Bax、Bcl－2、Mcl－1、caspase－3、γ－H2AX、NF－κB凋亡相关蛋白的表达。结果 TMZ作用于黑素瘤细胞后，能明显抑制黑素瘤细胞的生长，其抑制作用呈现明显的剂量依赖性效应。 Bax的表达量显著增加，Mcl－1、Bcl－2的表达量均有所降低，生成有活性的caspase－3；γ－H2AX的表达水平随TMZ作用时间的延长而上升，而NF－κB表达量减少，呈时间依赖性。结论 TMZ诱导黑素瘤细胞凋亡的机制可能与其对凋亡相关蛋白Bax、Bcl－2、Mcl－1、caspase－3、γ－H2AX、NF－κB的表达调控有关。Objective To observe the effects of temozolomide （ TMZ） on the apoptosis of three melanoma cell lines A375, MV3, and M14.Methods These cells were interfered with TMZ at exponential phase.Then, the inhibitory rate of the cells was assessed by CCK-8 assay.Furthermore, the quantities ofγ-H2AX, NF-κB, Bax, Mcl-1, Bcl-2, and caspase-3 were determined by Western blotting.Results The administration of TMZ could remarkably inhibit the growth of melanoma cells in a time-dependent manner.It could also result in an increased level of Bax, as well as de-creases in Mcl-1 and Bcl-2, and NF-κB, and activate caspase-3.The amount of γ-H2AX was increased along TMZ treatment extended.Conclusion TMZ can induce the apoptosis of melanoma cells, which may be related with its regulation of Bax, Bcl-2, Mcl-1, caspase-3,γ-H2AX and NF-κB.

关 键 词：替莫唑胺 黑素瘤 凋亡 

分 类 号：R73-34[医药卫生—肿瘤] R739.5[医药卫生—临床医学]