This yielded robust suppression of the miR-34a target genes CCND-1, Notch-1, Bcl-2, Survivin, and MDR-1, which reduced TNBC cell proliferation and induced cell cycle arrest.
Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)-6, which may be the underlying mechanism of hypoxia-induced tDRs that facilitate the doxorubicin resistance in TNBC.
These results reveal for the first time the involvement of the miRNA-449 family in doxorubicin resistance and their predictive and prognostic value in triple negative breast cancer patients.
Selected compounds (3-14, 16-29, 3a-7a, 9a, 13a, 13b, 14a, 14b, 16a, 17a, 24a, 35a) were evaluated for antiproliferative activity against three to five human tumor cell lines including triple-negative breast cancer (TNBC) and P-glycoprotein (P-gp) overexpressing multidrug-resistant (MDR) subline.
We found that TNBC cells characterized by high levels of Pgp and resistance to doxorubicin, had low induction of the ER-dependent pro-apoptotic factor C/EBP-β LIP upon doxorubicin treatment and high activities of lysosome and proteasome that constitutively destroyed LIP.
Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066.
Functionally, ectopic expression of miR-770 suppressed the doxorubicin-resistance of TNBC cell lines via regulation of apoptosis and tumor microenvironment, which was mediated by exosomes.
Our findings suggest that CXCL1 secreted by hAdSCs elicits doxorubicin resistance through miR-106a-mediated ABCG2 upregulation in triple negative breast cancer.
These findings indicate that P-gp inhibitors could sensitize TNBC cells to structurally and functionally diverse proteasome inhibitors and might provide new treatment strategy for TNBC..
Among recent alternative approaches being proposed, small interfering RNA (siRNA) gene therapy can potently suppress Bcl-2 proto-oncogene and p-glycoprotein gene expression, the most important chemotherapy resistance inducers in TNBC.