Abstract

PurposeTo explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo.MethodsThe 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.ResultsThe 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−1 L6H21 in 60 days.ConclusionOverall, 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.

Highlights

  • Breast cancer is one of the most common cancers affecting women worldwide [1]

  • We first used western blot assay to examined the expression of myeloid differentiation 2 (MD2) in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231 s and 4T1)

  • To explore the role of MD2 in breast cancer cells proliferation, we assessed the effects of inhibition of MD2 by L6H21 in 4T1 cells by MTT assay

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Summary

Introduction

Breast cancer is one of the most common cancers affecting women worldwide [1]. Despite intensive efforts and remarkable advances in the management of breast cancer, the physiological conditions that lead to tumorigenesis including breast cancer are not well understood and distant metastasis are still occurred in part of patients after treatments. It was reported that over 90% of the deaths of cancer patients are caused by metastasis [2]. Finding new modalities that treat the local and systemic components of the disease has become increasingly important. Toll like receptors (TLRs) belong to the pathogen recognition receptors (PRRs) family, which are essential components of innate immune system and serve as major contributor to chronic inflammation [3].

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