针对化疗耐药三阴性乳腺癌的新策略

Q2 Biochemistry, Genetics and Molecular Biology
Genes and Cancer Pub Date : 2020-07-22 eCollection Date: 2020-12-31 DOI:10.18632/genesandcancer.204
Jaganathan Venkatesh, Arun K Rishi, Kaladhar B Reddy
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引用次数: 4

摘要

我们小组和其他人之前的研究表明,目前的药物治疗策略可以消除大部分肿瘤细胞(非CSCs),但对癌症干细胞(CSCs)的影响很小,导致耐药性和肿瘤复发。我们研究了CFM-4.16 (CARP-1功能模拟物)和顺铂对四种三阴性乳腺癌(TNBC) MDA-MB-468、MDA-MB-231、CRL-2335和BR-1126、两种顺铂耐药CisR/MDA-231和CisR/MDA-468以及来自耐药细胞系的癌症干细胞(CSCs)的影响。CFM-4.16联合顺铂治疗TNBC细胞可抑制FZD8、LRP6和c-Myc的表达,与对照组相比,所有细胞系的细胞死亡均显著增加约70%-80%。当顺铂耐药CisR/MDA-231和CisR/MDA-468联合CFM-4.16治疗时,与对照组相比,它们也显示FZD8和LRP6降低,凋亡增加。同样,CFM-4.16联合顺铂治疗与对照组相比,使CSCs的乳腺球体形成能力降低了80-90%,增加了PARP的切割和凋亡。数据显示CFM-4.16联合顺铂治疗显著增加亲本、顺铂耐药和csc的凋亡/细胞死亡。综上所述,这些数据表明fzd8介导的wnt信号在介导CSCs生长和化疗耐药中起主要作用,其抑制增强了TNBC的化疗反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Novel strategies to target chemoresistant triple-negative breast cancer.

Novel strategies to target chemoresistant triple-negative breast cancer.

Novel strategies to target chemoresistant triple-negative breast cancer.

Novel strategies to target chemoresistant triple-negative breast cancer.

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.

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来源期刊
Genes and Cancer
Genes and Cancer Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
6
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