Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5

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 t...

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Autores principales: Xuemei Yang, Jialing Sun, Bin Wen, Yu Wang, Mingjia Zhang, Weicong Chen, Wenting Zhao, Chunyu He, Xiaodan Zhong, Yang Liu, Tong Li, Haitao Sun, Songqi He
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:859dd14da93849368281d126f25fce422021-12-01T06:38:04ZBiejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL51663-981210.3389/fphar.2021.771046https://doaj.org/article/859dd14da93849368281d126f25fce422021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.771046/fullhttps://doaj.org/toc/1663-9812Tumor-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.Xuemei YangXuemei YangJialing SunJialing SunBin WenYu WangMingjia ZhangWeicong ChenWenting ZhaoChunyu HeXiaodan ZhongYang LiuTong LiHaitao SunHaitao SunSongqi HeSongqi HeFrontiers Media S.A.articlehepatocellular carcinomatraditinal Chinese medicineCD8+T cellCCL5Biejiajian PillTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic hepatocellular carcinoma
traditinal Chinese medicine
CD8+T cell
CCL5
Biejiajian Pill
Therapeutics. Pharmacology
RM1-950
spellingShingle hepatocellular carcinoma
traditinal Chinese medicine
CD8+T cell
CCL5
Biejiajian Pill
Therapeutics. Pharmacology
RM1-950
Xuemei Yang
Xuemei Yang
Jialing Sun
Jialing Sun
Bin Wen
Yu Wang
Mingjia Zhang
Weicong Chen
Wenting Zhao
Chunyu He
Xiaodan Zhong
Yang Liu
Tong Li
Haitao Sun
Haitao Sun
Songqi He
Songqi He
Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5
description 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.
format article
author Xuemei Yang
Xuemei Yang
Jialing Sun
Jialing Sun
Bin Wen
Yu Wang
Mingjia Zhang
Weicong Chen
Wenting Zhao
Chunyu He
Xiaodan Zhong
Yang Liu
Tong Li
Haitao Sun
Haitao Sun
Songqi He
Songqi He
author_facet Xuemei Yang
Xuemei Yang
Jialing Sun
Jialing Sun
Bin Wen
Yu Wang
Mingjia Zhang
Weicong Chen
Wenting Zhao
Chunyu He
Xiaodan Zhong
Yang Liu
Tong Li
Haitao Sun
Haitao Sun
Songqi He
Songqi He
author_sort Xuemei Yang
title Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5
title_short Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5
title_full Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5
title_fullStr Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5
title_full_unstemmed Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5
title_sort biejiajian pill promotes the infiltration of cd8+ t cells in hepatocellular carcinoma by regulating the expression of ccl5
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/859dd14da93849368281d126f25fce42
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