Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells

被引：8

作者：

Jeong, Yun Soo ^{[1
]}

Lam, Thuy Giang ^{[1
]}

Jeong, Seho ^{[1
]}

Ahn, Sang-Gun ^{[1
]}

机构：

[1] Chosun Univ, Sch Dent, Dept Pathol, Gwangju 61452, South Korea

来源：

PHARMACEUTICALS | 2020年 / 13卷 / 09期

关键词：

metformin; HL156A; multidrug resistance; HOXC6; angiogenesis; NF-KAPPA-B; PROTEIN-KINASE ACTIVATOR; BREAST-CANCER; DRUG-RESISTANCE; PHOSPHOINOSITIDE; 3-KINASE; MDR1; EXPRESSION; 2-ACETYLAMINOFLUORENE; METABOLISM; MECHANISMS; INDUCTION;

D O I：

10.3390/ph13090218

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Multidrug resistance is a significant clinical crisis in cancer treatment and has been linked to the cellular expression of multidrug efflux transporters. The aim of this study was to examine the effects and mechanisms of the metformin derivative HL156A on human multidrug resistance (MDR) cancer cells. Here, HL156A significantly suppressed cell growth and colony formation through G2/M phase cell cycle arrest in MDR cancer cells. HL156A also reduced the wound closure rate and cell migration and induced caspase-3-dependent apoptosis. We found that HL156A inhibited the expression of MDR1 by inhibiting the HOXC6-mediated ERK1/2 signaling pathway and increased the sensitivity to paclitaxel or doxorubicin in MDR cells. Furthermore, HL156A significantly inhibited angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These results suggest the potential of the metformin derivative HL156A as a candidate therapeutic modality for the treatment of human multidrug-resistant cancers.

引用

页码：1 / 15

页数：16

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