Abstract：
:Chemotherapy resistance represents a major problem for the treatment of patients with lung carcinomas. Parthenolide (PN), a naturally occurring small molecule found in herb feverfew, has been used in clinical treatment. Although its importance in treating the chemotherapy resistance has been shown, the pharmacological benefits of PN for lung cancer with multidrug resistance are underappreciated. Using human lung epithelial carcinoma A549 and A549 derived DOX-resistant A549/DOX cell lines, we found that PN enhanced the apoptotic cytotoxicity of DOX in A549/DOX cells. PN inhibited P-glycoprotein (P-gp) up-regulation and promoted the intracellular accumulation of DOX in A549/DOX cells. PN also exhibited inhibitory effect on NF-κB activation in A549/DOX cells, suggesting that inhibition of NF-κB was involved in attenuating P-gp expression by PN. Moreover, we found that PN could also effectively inhibit the HSP70 up-regulation in A549/DOX cells. Further studies revealed a positive correlation between HSP70 and P-gp expression. Overexpression of HSP70 upregulated P-gp expression independently of NF-κB activation in A549 cells, and knockdown of HSP70 caused a reduced expression of P-gp in A549/DOX cells. RT-PCR experiments showed that HSP70 modulated the P-gp expression mainly at transcription level. Taken together, PN can reverse DOX resistance through suppressing P-gp expression by mechanisms involving attenuation of NF-κB activation and HSP70 up-regulation. Our results not only provide insight into potential use of PN in reversing P-gp mediated MDR to facilitate lung cancer chemotherapy, but also highlight a potential role of HSP70 in the development of drug resistance.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Xin Y,Yin F,Qi S,Shen L,Xu Y,Luo L,Lan L,Yin Zdoi
10.1016/j.toxlet.2013.06.215subject
Has Abstractpub_date
2013-08-14 00:00:00pages
73-82issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(13)01078-3journal_volume
221pub_type
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journal_title：Toxicology letters
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journal_title：Toxicology letters
pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章,评审
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2007.08.006
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(82)90259-4
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2006.12.003
更新日期：2007-02-28 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(99)00144-7
更新日期：1999-10-29 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.05.005
更新日期：2010-08-16 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.01.007
更新日期：2018-03-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.02.022
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journal_title：Toxicology letters
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(03)00113-9
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.03.015
更新日期：2018-06-01 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.06.240
更新日期：2013-09-12 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
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abstract：:In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.03.001
更新日期：2008-05-05 00:00:00
