自噬
阿霉素
生物
癌症研究
细胞凋亡
缺氧(环境)
乳腺癌
癌细胞
程序性细胞死亡
下调和上调
转录因子
MCF-7型
活力测定
癌症
化疗
基因
化学
人体乳房
生物化学
遗传学
有机化学
氧气
作者
C.M.T. Fourie,Manisha du Plessis,Justin Mills,Anna‐Mart Engelbrecht
标识
DOI:10.1016/j.yexcr.2022.113334
摘要
Oxygen deprivation is a key hallmark within solid tumours that contributes to breast-tumour pathophysiology. Under these conditions, neoplastic cells activate several genes, regulated by the HIF-1 transcription factor, which alters the tumour microenvironment to promote survival – including resistance to cell death in therapeutic attempts such as doxorubicin (Dox) treatment. We investigated HIF-1ɑ as a therapeutic target to sensitize breast cancer cells to Dox treatment. Under both normoxic (21% O2) and hypoxic (∼0.1% O2) conditions, the HIF-1 inhibitor, 2-methoxyestradiol (2-ME), was investigated as an adjuvant for its ability to alter MCF-7 cell viability, apoptosis, autophagy and molecular pathways which are often associated with increased cell survival. Here we observed that an inverse relationship between HIF-1ɑ and apoptosis exists and that Dox promotes autophagy under hypoxic conditions. Although adjuvant therapy with 2-ME induced an antagonistic effect in breast cancer cells, upregulated HIF-1ɑ expression in a hypoxic environment promotes treatment resistance and this was attenuated once HIF-1ɑ gene expression was silenced. Therefore, highlighting the identification of possible hypoxia-targeting therapies for breast cancer patients can be beneficial by promoting more favourable treatment responses.
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