Resistance to platinum-based chemotherapy in lung cancer cell lines.
Resistance to platinum-based chemotherapy in lung cancer cell lines.
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DOI：
10.1007/s00280-010-1268-2
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发表时间：
2010-11
影响因子：
3
通讯作者：
Simpkins, Henry
中科院分区：
文献类型：
--
作者：
Chen, Jianli;Emara, Nashwa;Solomides, Charalambos;Parekh, Hemant;Simpkins, Henry
对6种不同细胞来源的肺癌细胞系(包括小细胞肺癌和间皮瘤)进行了免疫组织化学鉴定，并研究了一系列与耐药有关的候选蛋白的作用。这些方法包括集落形成和细胞生长分析、免疫组织化学、siRNA敲除、实时定量聚合酶链式反应和蛋白质印迹。AKT、HO-1、HO-2、GRP78、14-3-3zeta和ERCC1水平与顺铂和奥沙利铂的细胞毒性无关，但与二氢二醇脱氢酶(DDH)的水平有关，DDH是一种先前与铂耐药有关的酶。这种关系似乎适用于那些来自肺上皮原发肿瘤的细胞系，但不适用于神经内分泌/小细胞和间皮瘤细胞系。制备了针对DDH-1和DDH-2的siRNA敲除，其中对顺铂抗性最强的细胞系(A549)的DDH亚型明显减少，实时定量聚合酶链式反应、蛋白质印迹杂交和酶活性检测表明。DDH-1基因敲除对顺铂的敏感性远高于DDH-2基因敲除。因此，上皮性肺癌细胞系对顺铂的敏感性似乎与DDH水平有关，其中DDH-1亚型产生的影响最大。结果与卵巢和其他细胞系的转染实验一致。
A series of six lung cancer cell lines of different cell origin (including small cell and mesothelioma) were characterized immunohistochemically and the role of a series of protein candidates previously implicated in drug resistance investigated. These include colony-forming and cell growth assays, immunohistochemistry, siRNA knockouts, Real Time PCR, and Western blots. No correlation was found with AKT, HO-1, HO-2, GRP78, 14-3-3zeta and ERCC1 levels and cisplatin nor oxaliplatin cytotoxicity but an association was observed with levels of the enzyme, dihydrodiol dehydrogenase (DDH); an enzyme previously implicated in the development of platinum resistance. The relationship appeared to hold true for those cell lines derived from lung epithelial primary tumors but not for the neuroendocrine/small cell and mesothelioma cell lines. siRNA knockouts to DDH-1 and DDH-2 were prepared with the cell line exhibiting the greatest resistance to cisplatin (A549) resulting in marked decreases in the DDH isoforms as assessed by Real Time PCR, western blot and enzymatic activity. The DDH-1 knockout was far more sensitive to cisplatin than the DDH-2 knockout. Thus, sensitivity to cisplatin appeared to be associated with DDH levels in epithelial lung cancer cell lines with the DDH-1 isoform producing the greatest effect. Results in keeping with transfection experiments with ovarian and other cell lines.
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影响因子：
3
作者：
Deng, HB;Adikari, M;Simpkins, H
通讯作者：
Simpkins, H
影响因子：
15.9
作者：
DABHOLKAR, M;VIONNET, J;REED, E
通讯作者：
REED, E
影响因子：
15.9
作者：
CHRISTEN, RD;JEKUNEN, AP;HOWELL, SB
通讯作者：
HOWELL, SB
影响因子：
4.8
作者：
Kweon, Mee-Hyang;Adhami, Vaqar Mustafa;Mukhtar, Hasan
通讯作者：
Mukhtar, Hasan
影响因子：
11.2
作者：
Fan, Tao;Li, Ruiyun;Jiang, Feng
通讯作者：
Jiang, Feng