ACT001 can prevent and reverse tamoxifen resistance in human breast cancer cell lines by inhibiting NF ‐κB activation

Tamoxifen simultaneously promotes apoptosis and activates the nuclear factor ‐κB (NF‐κB)–mediated antiapoptotic pathway, as a stress response, and that NF‐κB signaling and antiapoptotic gene expression are associated with tamoxifen resistance. AbstractEndocrine therapy is one of the main treatments for estrogen receptor –positive breast cancers. Tamoxifen is the most commonly used drug for endocrine therapy. However, primary or acquired tamoxifen resistance occurs in a large proportion of breast cancer patients, leading to therapeutic failure. We found that the combination of tamoxifen and ACT001, a nuclear facto r‐κB (NF‐κB) signaling pathway inhibitor, effectively inhibited the proliferation of both tamoxifen‐sensitive and tamoxifen‐resistant cells. The tamoxifen‐resistant cell line MCF7R/LCC9 showed active NF‐κB signaling and high apoptosis‐related gene transcription, especially for antia poptotic genes, which could be diminished by treatment with ACT001. These results demonstrate that ACT001 can prevent and reverse tamoxifen resistance by inhibiting NF‐κB activation.
Source: Journal of Cellular Biochemistry - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research