Sulforaphone enhances differentiation of memory precursor CD8+ cells by mTOR/ p-S6 signaling pathway
10.3872/j.issn.1007-385x.2018.09.012
- VernacularTitle:萝卜硫素通过p-mTOR/p-S6信号通路增强CD8+记忆细胞前体细胞的分化
- Author:
LI Hong
1
,
2
;
ZHANG Zhen
1
,
2
;
ZHOU Bin
3
;
LYU QuanJuna
3
;
ZHANG Yi
3
Author Information
1. (a. College of Public Health
2. b. Biotherapy Center of the FirstAffiliated Hospital, Zhengzhou University
3. b. Biotherapy Center of the FirstAffiliated Hospital, Zhengzhou University
- Publication Type:Journal Article
- Keywords:
sulforaphane (SFN);
p-mTOR/p-S6 signaling pathway;
memory CD8+T cell;
precursor cell
- From:
Chinese Journal of Cancer Biotherapy
2018;25(9):920-927
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of sulforaphane (SFN) on CD8+ T cells differentiation, phenotype and the secretion of intracellular cytokines, as well as to study the underlying molecular mechanism. Methods: In the in vitro culture experiment, the cells were categorized into control group, SNF 10 mmol/L group and SNF 20 mmol/L group according to the SNF concentration. The effect of SFN treatment on CD8+ T cells differentiation, phenotype and cytokine secretion were detected by flow cytometry, and the effect of mTOR siRNA on the expression of CD127 and LKRG1 in CD8+T cells was also detected by flow cytometry. Expression of Bcl-2 and Bcl-6 were analyzed by qRT-PCR. The effect of SFN on apoptosis of CD8+T cells was examined byAnnexin-V/PI staining. The protein expressions of p-mTOR, p-S6 and b-actin were detected by western blotting. Results: SFN significantly promoted the formation of memory precursor CD8+ T cells and decreased the expression level of PD-1 and Tim-3 in CD8+T cells(P<0.01); meanwhile, after the treatment of SFN, the expressions of anti-apoptosis genes Bcl-2 and Bcl-6 were significantly increased while the apoptosis of CD8+ T cells was significantly inhibited and the protein expressions of p-mTOR and p-S6 were also significantly inhibited(P<0.05 or P<0.01). Moreover, mTOR siRNA could significantly increasethe expression of CD127 and decrease the expression of LKRG1 (all P<0.01). Conclusion: Sulforaphone promotes the formation of memory precursor CD8+T cells possibly by inhibiting the p-mTOR signaling pathway, and this could obtain more T cells to provide new thoughts for clinical immunotherapy.
- Full text:20180912.pdf