Biejiajian Pill Promotes the Infiltration of CD8(+) T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5.
Biejiajian Pill Promotes the Infiltration of CD8(+) T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5.
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鳖甲煎丸通过调节CCL5表达促进肝细胞癌CD8 T细胞浸润
DOI：
10.3389/fphar.2021.771046
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发表时间：
2021
影响因子：
5.6
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Yang X;Sun J;Wen B;Wang Y;Zhang M;Chen W;Zhao W;He C;Zhong X;Liu Y;Li T;Sun H;He S
肿瘤浸润性CD8+T淋巴细胞大多与许多癌症（包括肝细胞癌（HCC））的良好预后相关。鳖甲煎丸是一种常用的中药，在我国被广泛应用于肝癌的治疗。以往的研究表明，BJJP抑制肝癌细胞的生长在体内和体外，通过对肿瘤细胞产生直接的细胞毒作用。本研究表明，除了直接的细胞毒性，BJJP抑制肿瘤细胞的生长，通过促进CD8+T细胞浸润到H22荷瘤小鼠的肿瘤。从机制上讲，趋化因子配体5（CCL5）被鉴定为BJJP治疗后体内肿瘤细胞最高表达的趋化因子之一。此外，CCL5在H22细胞中被敲低，结果显示该基因的敲低显著损害了体内CD8+T细胞的浸润。此外，在体外评估BJJP对人肝癌细胞系的作用。类似地，用BJJP处理的细胞具有更高的CCL5 mRNA表达，这与人肿瘤细胞中CCL5蛋白水平的增加一致。这些发现为BJJP的抗癌作用提供了新的见解，BJJP调节CCL5的表达和CD8+T细胞的浸润。因此，BJJP在临床上具有很大的应用潜力。
Tumor-infiltrating CD8+T lymphocytes are mostly associated with a favorable prognosis in numerous cancers, including hepatocellular carcinoma (HCC). Biejiajian Pill (BJJP) is a common type of traditional Chinese medicine that is widely used in the treatment of HCC in China. Previous studies showed that BJJP suppressed the growth of HCC cells both in vivo and in vitro, by exerting direct cytotoxic effects on tumor cells. The present study demonstrated that in addition to direct cytotoxicity, BJJP inhibits the growth of tumor cells by promoting the infiltration of CD8+T cells into the tumor in H22-bearing mice. Mechanistically, chemokine ligand 5 (CCL5) was identified as one of the most highly expressed chemokines by tumor cells in vivo after treatment with BJJP. Additionally, CCL5 was knocked down in H22 cells and the results showed that knockdown of the gene significantly impaired the infiltration of CD8+T cells in vivo. Furthermore, the effects of BJJP on human HCC cell lines were assessed in vitro. Similarly, cells treated with BJJP had higher expression of CCL5 mRNA, which was consistent with increased levels of CCL5 protein in human tumor cells. These findings provide new insights into the anticancer effects of BJJP, which regulated the expression of CCL5 and the infiltration of CD8+T cells. The results, therefore, suggest that BJJP has great potential application in clinical practice.
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