Differential drug resistance acquisition to doxorubicin and paclitaxel in breast cancer cells.
Differential drug resistance acquisition to doxorubicin and paclitaxel in breast cancer cells.
复制标题
乳腺癌细胞对阿霉素和紫杉醇的差异耐药性获得
DOI：
10.1186/s12935-014-0142-4
复制
发表时间：
2014
影响因子：
5.8
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Xu F;Wang F;Yang T;Sheng Y;Zhong T;Chen Y
已有研究表明，多种信号转导途径参与了抗癌药物诱导的多药耐药（MDR）过程，但有证据表明，不同药物对P-gp表达和活性的调节并不相同，甚至不一致。为了进一步说明这种药物特异性作用，以时间依赖性方式研究了使乳腺癌细胞MCF-7获得对紫杉醇（PTX）或阿霉素（DOX）的MDR的可能机制。结果表明，至少有两条途径参与了这一过程。一是NF-κB的短暂短暂激活，二是PXR的相对延长诱导。PXR和NF-κB通路均参与了PTX耐药的获得，而DOX对PXR介导的P-gp诱导无明显影响。此外，DOX和PTX对NF-κB的激活特性也不尽相同。本研究表明，阿霉素的获得性耐药是通过或部分通过NF-κB活化而不是其上游受体TLR 4的活化，而紫杉醇可通过TLR 4-NF-κB途径诱导耐药。据我们所知，该报告是第一个直接比较NF-κB和PXR途径的时间依赖性的报告。目前的研究提供了有用的洞察力的不同能力的DOX和PTX诱导P-gp介导的多药耐药乳腺癌。在不同的抗癌药物存在下，可能需要不同的策略来规避MDR。本文的在线版本（doi：10.1186/s12935-014-0142-4）包含补充材料，可供授权用户使用。
Several signal transduction pathways have been reported being involved in the acquisition of P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) upon exposure to anti-cancer drugs, whereas there is evidence indicating that the expression and activity of P-gp were not equally or even reversely modulated by different drugs. To further illustrate this drug-specific effect, possible mechanisms that enable breast cancer cells MCF-7 to acquire MDR to either paclitaxel (PTX) or doxorubicin (DOX) were investigated in a time-dependent manner. The results suggested that at least two pathways participated in this process. One was the short and transient activation of NF-κB, the second one was the relatively prolonged induction of PXR. Both PXR and NF-κB pathways took part in the PTX drug resistance acquisition, whereas DOX did not exert a significant effect on the PXR-mediated induction of P-gp. Furthermore, the property of NF-κB activation shared by DOX and PTX was not identical. An attempt made in the present study demonstrated that the acquired resistance to DOX was via or partially via NF-κB activation but not its upstream receptor TLR4, while PTX can induce the drug resistance via TLR4-NF-κB pathway. To our knowledge, this report is among the first to directly compare the time dependence of NF-κB and PXR pathways. The current study provides useful insight into the distinct ability of DOX and PTX to induce P-gp mediated MDR in breast cancer. Different strategies may be required to circumvent MDR in the presence of different anti-cancer drugs. The online version of this article (doi:10.1186/s12935-014-0142-4) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.1
作者：
Choi, Hye Jin;Kim, Juil;Moon, Yuseok
通讯作者：
Moon, Yuseok
影响因子：
3
作者：
Harmsen, Stefan;Meijerman, I.;Febus, C. L.;Maas-Bakker, R. F.;Beijnen, J. H.;Schellens, J. H. M.
通讯作者：
Schellens, J. H. M.
影响因子：
6
作者：
Bao, Lili;Hazari, Sidhartha;Dash, Srikanta
通讯作者：
Dash, Srikanta
影响因子：
11.2
作者：
Kelly, MG;Alvero, AB;Mor, G
通讯作者：
Mor, G
人乳腺肿瘤细胞中的酸化不足及其对化学疗法的影响。
影响因子：
15.3
作者：
Altan, N;Chen, Y;Schindler, M;Simon, S M
通讯作者：
Simon, S M