Novel strategies to target chemoresistant triple-negative breast cancer.

Autor:	Venkatesh J; John D. Dingell VA Medical Center, Wayne State University, Detroit, MI, USA.; Department of Oncology, Wayne State University, Detroit, MI, USA., Rishi AK; John D. Dingell VA Medical Center, Wayne State University, Detroit, MI, USA.; Department of Oncology, Wayne State University, Detroit, MI, USA.; Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA., Reddy KB; Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.; Department of Pathology, Wayne State University, Detroit, MI, USA.
Jazyk:	angličtina
Zdroj:	Genes & cancer [Genes Cancer] 2020 Jul 22; Vol. 11 (3-4), pp. 95-105. Date of Electronic Publication: 2020 Jul 22 (Print Publication: 2020).
DOI:	10.18632/genesandcancer.204
Abstrakt:	Previous studies from our group and others have shown that current drug treatment(s) strategies eliminate bulk of tumor cells (non-CSCs) but it had a minimal effect on cancer stem cells (CSCs) leading to resistance and tumor recurrence. We studied the effects of CFM-4.16 (CARP-1 functional mimetic) and/or cisplatin on four Triple-negative breast cancer (TNBC) MDA-MB-468, MDA-MB-231, CRL-2335 and BR-1126, two cisplatin resistant CisR/MDA-231 and CisR/MDA-468 and cancer stem cells (CSCs) from resistant cell lines. TNBC cells treated with CFM-4.16 plus cisplatin inhibited the expression of FZD8, LRP6 and c-Myc and significantly enhanced cell death in all the cell lines by ~70%-80% compared with the control(s). When Cisplatin resistant CisR/MDA-231 and CisR/MDA-468 were treated with CFM-4.16 plus cisplatin, they also showed a reduction in FZD8 and LRP6 and increased apoptosis compared to control group. Similarly, CFM-4.16 plus cisplatin treatment reduced mammospheres formation abilities of CSCs by 80-90% compared to control group, increased PARP cleavage and apoptosis. Data shows CFM-4.16 plus cisplatin treatment significantly increased apoptosis/cell death in parental, cisplatin resistant and CSCs. Taken together the data suggests that FZD8-mediated Wnt-signaling plays a major role in mediating CSCs growth and resistance to chemotherapy and its inhibition enhances the chemotherapeutic response in TNBC. Competing Interests: CONFLICT OF INTEREST The authors declare that they have no competing interests. (Copyright: © 2020 Venkatesh et al.)
Databáze:	MEDLINE
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