Bisphenol A at low nanomolar doses confers chemoresistance in estrogen receptor-alpha-positive and -negative breast cancer cells.
Bisphenol A at low nanomolar doses confers chemoresistance in estrogen receptor-alpha-positive and -negative breast cancer cells.
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DOI：
10.1289/ehp.11788
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发表时间：
2009-02
影响因子：
10.4
通讯作者：
Ben-Jonathan N
中科院分区：
文献类型：
--
作者：
Lapensee EW;Tuttle TR;Fox SR;Ben-Jonathan N
对化疗的耐药性是乳腺癌患者面临的一个主要问题，确定化疗耐药性的潜在因素是一个关键的研究领域。双酚A（BPA）长期以来一直被怀疑会促进致癌作用，但许多研究中使用的高剂量BPA产生了相互矛盾的结果。此外，BPA发挥其生物作用的机制尚不清楚。虽然雌激素已被证明可以拮抗抗癌药物，但BPA在化疗耐药性中的作用尚未得到研究。本研究的目的是确定低纳摩尔浓度的BPA是否对抗雌激素受体-α（ERα）阳性T47 D和ERα阴性MDA-MB-468乳腺癌细胞中阿霉素、顺铂和长春碱的作用。我们使用3-（4，5-二甲基噻唑-2-基）2，5-二苯基溴化四氮唑（MTT）细胞毒性试验测定细胞对抗癌药物和BPA的反应性。特异性ERα和ERβ抑制剂和实时聚合酶链反应用于鉴定介导BPA作用的潜在受体。通过Western印迹法评估抗凋亡蛋白的表达。BPA拮抗多种化疗药物对ERα阳性和阴性乳腺癌细胞的细胞毒性，而不依赖于经典的ER。这两种细胞类型表达替代ER，包括G蛋白偶联受体30（GPR 30）和雌激素相关受体家族的成员。抗凋亡蛋白表达的增加是BPA发挥其抗细胞毒性作用的潜在机制。环境相关剂量的BPA会降低化疗药物的功效。这些数据为BPA对人类健康有害的证据提供了相当大的支持。
Resistance to chemotherapy is a major problem facing breast cancer patients, and identifying potential contributors to chemoresistance is a critical area of research. Bisphenol A (BPA) has long been suspected to promote carcinogenesis, but the high doses of BPA used in many studies generated conflicting results. In addition, the mechanism by which BPA exerts its biological actions is unclear. Although estrogen has been shown to antagonize anticancer drugs, the role of BPA in chemoresistance has not been examined. The objective of our study was to determine whether BPA at low nanomolar concentrations opposes the action of doxorubicin, cisplatin, and vinblastine in the estrogen receptor-α (ERα)-positive T47D and the ERα-negative MDA-MB-468 breast cancer cells. We determined the responsiveness of cells to anticancer drugs and BPA using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay. Specific ERα and ERβ inhibitors and real-time polymerase chain reaction were used to identify potential receptor(s) that mediate the actions of BPA. Expression of antiapoptotic proteins was assessed by Western blotting. BPA antagonizes the cytotoxicity of multiple chemotherapeutic agents in both ERα-positive and -negative breast cancer cells independent of the classical ERs. Both cell types express alternative ERs, including G-protein–coupled receptor 30 (GPR30) and members of the estrogen-related receptor family. Increased expression of antiapoptotic proteins is a potential mechanism by which BPA exerts its anticytotoxic effects. BPA at environmentally relevant doses reduces the efficacy of chemotherapeutic agents. These data provide considerable support to the accumulating evidence that BPA is hazardous to human health.
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影响因子：
5.1
作者：
Chen, X;Carystinos, GD;Batist, G
通讯作者：
Batist, G
影响因子：
4.8
作者：
Kuiper, GGJM;Lemmen, JG;Gustafsson, JÄ
通讯作者：
Gustafsson, JÄ
影响因子：
3.3
作者：
Fernandez, M. F.;Arrebola, J. P.;Olea, N.
通讯作者：
Olea, N.
DOI：
10.1016/j.bbrc.2003.12.194
发表时间：
2004-02-20
影响因子：
3.1
作者：
Huppunen, J;Aarnisalo, P
通讯作者：
Aarnisalo, P
DOI：
10.1034/j.1600-0773.2003.920408.x
发表时间：
2003-04-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
Olsen, CM;Meussen-Elholm, ETM;Hongslo, JK
通讯作者：
Hongslo, JK