ZLM-7 Blocks Breast Cancer Progression by Inhibiting MDM2 via Upregulation of 14-3-3 Sigma

被引：2

作者：

Wen, Min ^{[1
,2
]}

Zou, Zi-Zheng ^{[1
,2
]}

Luo, Tiao ^{[3
]}

Li, Xuan ^{[1
]}

Liu, Su-You ^{[4
]}

Li, Ji-Jia ^{[5
,6
,7
]}

Luo, Zhi-Yong ^{[1
]}

机构：

[1] Cent South Univ, Sch Life Sci, Xiangya Sch Med,Hunan Prov Key Lab Basic & Appl H, Hunan Key Lab Anim Models Human Dis,Dept Biochem, Changsha 410008, Peoples R China

[2] Yiyang Med Coll, Dept Biochem & Mol Biol, Yiyang 413000, Peoples R China

[3] Cent South Univ, Xiangya Stomatol Hosp, Xiangya Sch Stomatol, Hunan Key Lab Oral Hlth Res, Changsha 410008, Peoples R China

[4] Cent South Univ, Sch Pharmaceut Sci, Dept Med Chem, Changsha 410006, Peoples R China

[5] Cent South Univ, Xiangya Hosp, Ctr Stomatol, Changsha 410008, Peoples R China

[6] Cent South Univ, Xiangya Hosp, Res Ctr Oral & Maxillofacial Tumor, Changsha 410008, Peoples R China

[7] Cent South Univ, Inst Oral Canc & Precanc Les, Changsha 410008, Peoples R China

来源：

PHARMACEUTICALS | 2022年 / 15卷 / 07期

基金：

中国国家自然科学基金;

关键词：

breast cancer; ZLM-7; 14-3-3; sigma; MDM2; cell cycle; COMBRETASTATIN A-4; APOPTOSIS; P53; HYPERMETHYLATION; ANGIOGENESIS; PROTEINS; PATHWAY; ANALOGS; COMPLEX; ARREST;

D O I：

10.3390/ph15070874

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Breast cancer is one of the most prevalent malignancies with poor prognosis. Inhibition of angiogenesis is becoming a valid and evident therapeutic strategy to treat cancer. Recent studies uncovered the antiangiogenic activity of ZLM-7 (a combretastain A-4 derivative), but the regulatory mechanism is unclear. ZLM-7 treatment was applied in estrogen receptor-positive cell MCF-7, triple-negative breast cancer cell MDA-MB-231 and xenograft models. Transfections were conducted to overexpress or knockdown targeted genes. The gene and protein expressions were measured by qPCR and Western blotting assay, respectively. Cell proliferation and apoptosis were evaluated using the CCK8 method, clone formation assay and flow cytometry. We found that ZLM-7 upregulated 14-3-3 sigma expression but downregulated MDM2 expression in breast cancer cells. ZLM-7 delayed cell proliferation, promoted apoptosis and blocked cell-cycle progression in human breast cancer cells in vitro, while those effects were abolished by 14-3-3 sigma knockdown; overexpression of 14-3-3 sigma reproduced the actions of ZLM-7 on the cell cycle, which could be reversed by MDM2 overexpression. In xenograft models, ZLM-7 treatment significantly inhibited tumor growth while the inhibition was attenuated when 14-3-3 sigma was silenced. Collectively, ZLM-7 could inhibit MDM2 via upregulating 14-3-3 sigma expression, thereby blocking the breast cancer progression.

引用

页数：15