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<p>Our study aims to explore the suppression effect of ML385 on hypoxia-induced chemoresistance and stemness in MDA-MB-231 cells. The stem-cell-like phenotype was determined via sphere formation assay by the number of spheres whose diameter is longer than 70 m; the RNA and protein levels of stemness markers (<i>Notch1</i>, <i>Sox9</i>, <i>Nanog</i>, and <i>Oct4</i>) were detected by RT-PCR and western blot, separately; CCK-8 assay was carried out to investigate the cell viability after treatment with chemotherapeutic drugs (adriamycin, cisplatin, and olaparib). Compared with a normoxic condition, culturing under the hypoxia condition not only augmented the ability of MDA-MB-231 cells against chemotherapeutic agents but also caused up-regulation of stemness markers at both RNA and protein levels. Moreover, hypoxia sensibly elevated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) along with heme oxygenase-1 (HO-1), and decreased ROS production in MDA-MB-231 cells, which is reversed by the treatment of ML385. Further, ML385 effectively decreased the hypoxia-induced chemoresistance and stemness of MDA-MB-231 cells in a dose-dependent manner, which could be abolished by the knockdown of Nrf2. ML385 can suppress hypoxia-induced drug-resistance and cancer stemness of breast cancer cells by blocking the Nrf2/HO-1 pathway, which innovatively suggests the therapeutic potential of ML385 on breast cancer.</p>

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ML385 Suppresses Hypoxia-Induced Drug Resistance and Cancer Stemness of Breast Cancer Cells by Blocking the Nrf2/HO-1 Pathway

  • 期刊论文

  • 发表日期：

    2025年1月1日

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  • Huan Yang,
  • Wentian Zheng,
  • Hehua Lin,
  • Hanxing Huang

摘要

Our study aims to explore the suppression effect of ML385 on hypoxia-induced chemoresistance and stemness in MDA-MB-231 cells. The stem-cell-like phenotype was determined via sphere formation assay by the number of spheres whose diameter is longer than 70 m; the RNA and protein levels of stemness markers (Notch1, Sox9, Nanog, and Oct4) were detected by RT-PCR and western blot, separately; CCK-8 assay was carried out to investigate the cell viability after treatment with chemotherapeutic drugs (adriamycin, cisplatin, and olaparib). Compared with a normoxic condition, culturing under the hypoxia condition not only augmented the ability of MDA-MB-231 cells against chemotherapeutic agents but also caused up-regulation of stemness markers at both RNA and protein levels. Moreover, hypoxia sensibly elevated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) along with heme oxygenase-1 (HO-1), and decreased ROS production in MDA-MB-231 cells, which is reversed by the treatment of ML385. Further, ML385 effectively decreased the hypoxia-induced chemoresistance and stemness of MDA-MB-231 cells in a dose-dependent manner, which could be abolished by the knockdown of Nrf2. ML385 can suppress hypoxia-induced drug-resistance and cancer stemness of breast cancer cells by blocking the Nrf2/HO-1 pathway, which innovatively suggests the therapeutic potential of ML385 on breast cancer.