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茶多酚通过下调 TLR4 抑制黑色素瘤细胞的增殖、迁移和侵袭。

Tea polyphenols inhibit the proliferation, migration, and invasion of melanoma cells through the down-regulation of TLR4.

机构信息

1 Department of Dermatology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

2 Department of Cardiac Surgical Care Unit, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

出版信息

Int J Immunopathol Pharmacol. 2018 Jan-Dec;32:394632017739531. doi: 10.1177/0394632017739531.

Abstract

Melanoma is the most common skin cancer and malignant melanoma which can cause skin cancer-related deaths. Toll-like receptor 4 (TLR4) had been reported to play an important role in melanoma, and tea polyphenol (TP) is regarded as an anticancer substance. However, the relationship between TP and TLR4 in melanoma is not well explored. Therefore, our aim is to figure out how TP has an influence on melanoma. Melanoma cell lines (B16F10 and A375) were treated with TP and lipopolysaccharides (LPS). Western blot assay was used to examine TLR4 expression, and MTT assay was conducted to assess proliferation. Wound healing assay was conducted to evaluate the migration of melanoma cells, and transwell assay was used to examine the melanoma cells' invasiveness. Besides, in vivo experiments were practiced for TP function in mice with melanoma cells. TP inhibited the proliferation, migration and invasion ability of melanoma cells, which displayed a dosage and time dependence. TLR4 was highly expressed in melanoma cells compared with normal skin cells. TP could suppress TLR4 expression both in normal melanomas and in stimulated melanomas by TLR4 agonist LPS. Suppressing TLR4 in melanomas could inhibit cell function (proliferation, migration, and invasion), and blocking the expression of 67LR could abolish TP function on TLR4. TP can inhibit melanoma (B16F10) growth in vivo.

摘要

黑色素瘤是最常见的皮肤癌,恶性黑色素瘤可导致与皮肤癌相关的死亡。Toll 样受体 4(TLR4)已被报道在黑色素瘤中发挥重要作用,而茶多酚(TP)被认为是一种抗癌物质。然而,TP 和 TLR4 之间在黑色素瘤中的关系尚未得到充分探索。因此,我们的目的是探讨 TP 如何影响黑色素瘤。用 TP 和脂多糖(LPS)处理黑色素瘤细胞系(B16F10 和 A375)。采用 Western blot 检测 TLR4 表达,MTT 检测评估增殖。划痕愈合实验评估黑色素瘤细胞的迁移,Transwell 实验检测黑色素瘤细胞的侵袭能力。此外,还在携带黑色素瘤细胞的小鼠中进行了体内实验以研究 TP 的功能。TP 抑制黑色素瘤细胞的增殖、迁移和侵袭能力,呈剂量和时间依赖性。与正常皮肤细胞相比,黑色素瘤细胞中 TLR4 表达较高。TP 可抑制 TLR4 激动剂 LPS 刺激的正常和刺激的黑色素瘤细胞中 TLR4 的表达。抑制黑色素瘤细胞中的 TLR4 可抑制细胞功能(增殖、迁移和侵袭),阻断 67LR 的表达可消除 TP 对 TLR4 的作用。TP 可抑制体内黑色素瘤(B16F10)的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f30/5849249/8449a6680891/10.1177_0394632017739531-fig1.jpg

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