3,3'-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants.

3,3'-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants.
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DOI:
10.1016/j.canlet.2010.02.014
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发表时间:
2010-09-01
期刊:
影响因子:
9.7
通讯作者:
Tang, Careen K.
Tang, Careen K.
中科院分区:
医学1区
文献类型:
--
作者:
Rahimi, Massod;Huang, Kai-Ling;Tang, Careen K.

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表皮生长因子受体(EGFR)突变体与化疗、放疗和靶向治疗的耐药性有关。本研究发现,植物化学物质3,3′-二吲哚基甲烷(DIM)可以抑制乳腺癌、胶质瘤和非小细胞肺癌细胞的生长和侵袭,而与表达哪种EGFR突变体和耐药表型无关。DIM降低了一系列生长因子信号通路,改变了细胞周期调节因子和凋亡蛋白,有利于细胞周期阻滞和凋亡。因此,DIM可能用于抑制癌细胞生长和侵袭的治疗方案中,并有可能克服EGFR突变体相关的耐药性。
Epidermal Growth Factor Receptor (EGFR) mutants are associated with resistance to chemotherapy, radiation, and targeted therapies. Here we found that the phytochemical 3,3′-Diindolylmethane (DIM) can inhibit the growth and also the invasion of breast cancer, glioma, and non-small cell lung cancer cells regardless of which EGFR mutant is expressed and the drug-resistant phenotype. DIM reduced an array of growth factor signaling pathways and altered cell cycle regulators and apoptotic proteins favoring cell cycle arrest and apoptosis. Therefore, DIM may be used in treatment regimens to inhibit cancer cell growth and invasion, and potentially overcome EGFR mutant-associated drug resistance.
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