ZLM-7 Blocks Breast Cancer Progression by Inhibiting MDM2 via Upregulation of 14-3-3 Sigma.
ZLM-7 Blocks Breast Cancer Progression by Inhibiting MDM2 via Upregulation of 14-3-3 Sigma.
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ZLM-7 通过上调 14-3-3 Sigma 抑制 MDM2 来阻止乳腺癌进展
DOI：
10.3390/ph15070874
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发表时间：
2022-07-15
期刊：
影响因子：
4.6
通讯作者：
Luo, Zhi-Yong
中科院分区：
文献类型：
--
作者：
Wen, Min;Zou, Zi-Zheng;Luo, Tiao;Li, Xuan;Liu, Su-You;Li, Ji-Jia;Luo, Zhi-Yong
乳腺癌是最常见的恶性肿瘤之一，预后较差。抑制血管生成正在成为治疗癌症的有效且明显的治疗策略。最近的研究揭示了 ZLM-7（combretatain A-4 衍生物）的抗血管生成活性，但其调节机制尚不清楚。 ZLM-7治疗应用于雌激素受体阳性细胞MCF-7、三阴性乳腺癌细胞MDA-MB-231和异种移植模型。进行转染以过度表达或敲低目标基因。分别通过qPCR和Western blotting测定基因和蛋白表达。使用CCK8方法、克隆形成测定和流式细胞术评估细胞增殖和凋亡。我们发现 ZLM-7 上调乳腺癌细胞中 14-3-3 sigma 表达，但下调 MDM2 表达。 ZLM-7 在体外延迟人乳腺癌细胞的细胞增殖、促进细胞凋亡并阻断细胞周期进程，而这些作用可通过 14-3-3 sigma 敲低而消除； 14-3-3 sigma 的过度表达再现了 ZLM-7 对细胞周期的作用，这种作用可以通过 MDM2 过度表达来逆转。在异种移植模型中，ZLM-7 治疗显着抑制肿瘤生长，而当 14-3-3 sigma 沉默时，抑制作用减弱。总的来说，ZLM-7 可以通过上调 14-3-3 sigma 表达来抑制 MDM2，从而阻止乳腺癌进展。
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.
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ZLM-7通过miR-212-3p/Sp1/VEGFA信号轴抑制乳腺癌的发生和血管生成
DOI：
10.1186/s10020-020-00239-2
发表时间：
2020-11-13
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
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Li X;Zou ZZ;Wen M;Xie YZ;Peng KJ;Luo T;Liu SY;Gu Q;Li JJ;Luo ZY
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Luo ZY
影响因子：
7
作者：
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通讯作者：
Doveston RG
影响因子：
3.7
作者：
Ravi D;Chen Y;Karia B;Brown A;Gu TT;Li J;Carey MS;Hennessy BT;Bishop AJ
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Bishop AJ
影响因子：
16.6
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Phan L;Chou PC;Velazquez-Torres G;Samudio I;Parreno K;Huang Y;Tseng C;Vu T;Gully C;Su CH;Wang E;Chen J;Choi HH;Fuentes-Mattei E;Shin JH;Shiang C;Grabiner B;Blonska M;Skerl S;Shao Y;Cody D;Delacerda J;Kingsley C;Webb D;Carlock C;Zhou Z;Hsieh YC;Lee J;Elliott A;Ramirez M;Bankson J;Hazle J;Wang Y;Li L;Weng S;Rizk N;Wen YY;Lin X;Wang H;Wang H;Zhang A;Xia X;Wu Y;Habra M;Yang W;Pusztai L;Yeung SC;Lee MH
通讯作者：
Lee MH
影响因子：
16
作者：
Hermeking, H;Lengauer, C;Vogelstein, B
通讯作者：
Vogelstein, B