Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, 325000, Zhejiang, China.
Department of Breast Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Lucheng District, Wenzhou, 325000, Zhejiang, China.
Clin Transl Oncol. 2021 Sep;23(9):1811-1817. doi: 10.1007/s12094-021-02587-9. Epub 2021 Mar 17.
To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo.
The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231 s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and trans-well matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo.
The expression of MD2 is much higher in MDA-MB-231 s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (p < 0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significantly improved survival of 4T1-bearing mice (p < 0.05). Additionally, we also observed that none of the mice died from the toxic effect of 10 mg kg L6H21 in 60 days.
Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.
探讨靶向髓样分化因子 2（MD2）的干预措施对乳腺癌体外和体内进展的影响。
采用 Western blot 检测正常乳腺细胞（Hs 578Bst）和三种乳腺癌细胞系（MCF-7、MDA-MB-231 和 4T1）中 MD2 的表达。MTT 法检测 L6H21 处理后 4T1 细胞的增殖，划痕愈合试验和 Transwell 基质胶侵袭试验分别检测细胞迁移和侵袭。此外，为进一步研究 MD2 在肿瘤进展中的作用，我们评估了抑制 MD2 对体内异种移植肿瘤进展的影响。
与正常乳腺细胞（Hs 578Bst）或 MCF-7 细胞相比，MD2 在 MDA-MB-231 和 4T1 细胞中的表达明显更高（p<0.05）。体外，L6H21 抑制 MD2 呈剂量依赖性地显著抑制 4T1 细胞的增殖、迁移和侵袭。体内，L6H21 预处理显著提高了荷 4T1 小鼠的存活率（p<0.05）。此外，我们还观察到在 60 天内，没有一只小鼠因 10mg/kg L6H21 的毒性作用而死亡。
综上所述，这项工作表明抑制 MD2 在体外显示出进展抑制作用，并显著延长体内存活时间。这些发现为将 MD2 作为乳腺癌治疗靶点提供了潜在的实验依据。
