Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIα expression
Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIα expression
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DOI：
10.1016/s0360-3016(02)03037-7
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发表时间：
2002-11-01
影响因子：
7
通讯作者：
Davey, RA
中科院分区：
文献类型：
--
作者：
Henness, S;Davey, MW;Davey, RA
目的：小细胞肺癌（SCLC）在接受化疗和放疗的标准治疗后，通常会对两种治疗产生耐药性。我们的目的是建立如果分割放射治疗单独会诱导辐射和耐药性的H69小细胞肺癌细胞株，并确定的机制resistance.Methods和材料：H69小细胞肺癌细胞进行了处理，用分割X射线的累积剂量为37.5戈伊超过8个月，产生的H69/R38亚系。使用MTT（3，-4，5二甲基噻唑-2，5二苯基四唑溴化物）细胞活力测定来确定药物和辐射抗性。结果：H69/R38亚系对放射（2.0 +/-0.2-倍，p < 0.0001）、顺铂（14 +/-7-倍，p <0.001）、柔红霉素（6 +/-3-倍，p < 0.05）和诺维本（1.7 +/-0.15-倍，p < 0.02）具有抗性。这与多药耐药相关蛋白MRP 1和MRP 2以及拓扑异构酶II α的表达增加，谷胱甘肽-S-转移酶pi（GSTpi）和bcl-2的表达减少以及顺铂蓄积减少有关。用4戈伊的X射线处理在H69细胞中产生66%的MRP 2降低，而在H69/R38细胞中没有变化。这种治疗也造成了5倍的增加拓扑异构酶II α在H69/R38细胞相比，增加了1.5倍，在H69 cells.Conclusions：分割辐射单独可以导致发展稳定的辐射和耐药性，并在小细胞肺癌细胞辐射反应的改变。(C)2002年爱思唯尔科技有限公司
Purpose: After standard treatment with chemotherapy and radiotherapy, small-cell lung cancer (SCLC) often develops resistance to both treatments. Our aims were to establish if fractionated radiation treatment alone would induce radiation and drug resistance in the H69 SCLC cell line, and to determine the mechanisms of resistance.Methods and Materials: H69 SCLC cells were treated with fractionated X-rays to an accumulated dose of 37.5 Gy over 8 months to produce the H69/R38 subline. Drug and radiation resistance was determined using the MTT (3,-4,5 dimethylthiazol-2,5 diphenyltetrazolium bromide) cell viability assay. Protein expression was analyzed by Western blot.Results: The H69/R38 subline was resistant to radiation (2.0 +/- 0.2-fold, p < 0.0001), cisplatin (14 +/- 7-fold, p < 0.001), daunorubicin (6 +/- 3-fold, p < 0.05), and navelbine (1.7 +/- 0.15-fold, p < 0.02). This was associated with increased expression of the multidrug resistance-associated proteins, MRP1 and MRP2, and topoisomerase IIalpha and decreased expression of glutathione-S-transferase pi (GSTpi) and bcl-2 and decreased cisplatin accumulation. Treatment with 4 Gy of X-rays produced a 66% decrease in MRP2 in the H69 cells with no change in the H69/R38 cells. This treatment also caused a 5-fold increase in topoisomerase IIalpha in the H69/R38 cells compared with a 1.5-fold increase in the H69 cells.Conclusions: Fractionated radiation alone can lead to the development of stable radiation and drug resistance and an altered response to radiation in SCLC cells. (C) 2002 Elsevier Science Inc.