SRM Research Institute and Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India.
Iran J Immunol. 2021 Jun;18(2):111-118. doi: 10.22034/iji.2021.85430.1710.
Breast cancer is an uncontrolled growth of epithelial cells. The loss of Breast Cancer gene1 (BRCA1) activity due to mutation or down-regulation of gene expression promotes tumorigenesis and increases the risk of breast cancer.
We aimed to pulsate lymphocytes of breast cancer patients and normal individuals, using Diospyros peregrina fruit preparation (DFP) to study the cancer-protective immunity, and the signal transduction processes involved with it. We also investigated the role of DFP in the release of lymphocytic nitric oxide (NO), which is a key tumoricidal agent, known to regulate T-cell proliferation, cytokine production, cell signaling, and apoptosis.
Using Ficoll-Hypaque gradient centrifugation, lymphocytes were isolated from the blood of 12 patients and 12 normal individuals. Cells were treated with or without DFP (2.5 µg/ml) for 48 hours. Both non-stimulated and stimulated cells were then subjected to MTT and NO release assay; following which qPCR was performed to estimate mRNA levels and percentage enrichment of certain genes.
DFP stimulates lymphocytic proliferation (p=0.0118) and release of NO (p=0.01) significantly. DFP also noticeably enhances the expression of T helper (TH) cell 1 specific interferon-gamma (IFNG), interleukin 12 (IL12), T-Box Transcription Factor 21 (TBX21) and signal transducer and activator of transcription 1 (STAT1) genes. DFP treatment significantly increases tumor protective immunity by decreasing the expression levels of TH2 network-specific GATA3 and interleukin 4 (IL4) genes but increasing the expression levels of TH1 network-specific IFNG, IL12, TBX21, and STAT1 genes.
DFP increases the expression levels of TH1 specific network genes which in turn help in evoking tumor protective immunity.
乳腺癌是上皮细胞不受控制的生长。乳腺癌基因 1（BRCA1）的活性丧失由于突变或基因表达下调促进肿瘤发生并增加乳腺癌的风险。
我们旨在使用南酸枣果实制剂（DFP）脉冲处理乳腺癌患者和正常个体的淋巴细胞，以研究其抗癌免疫作用及其涉及的信号转导过程。我们还研究了 DFP 在淋巴细胞一氧化氮（NO）释放中的作用，NO 是一种关键的杀肿瘤剂，已知其调节 T 细胞增殖、细胞因子产生、细胞信号转导和细胞凋亡。
使用 Ficoll-Hypaque 梯度离心法从 12 名患者和 12 名正常个体的血液中分离淋巴细胞。细胞用或不用 DFP（2.5μg/ml）处理 48 小时。然后将未刺激和刺激的细胞进行 MTT 和 NO 释放测定；之后进行 qPCR 以估计某些基因的 mRNA 水平和富集百分比。
DFP 显著刺激淋巴细胞增殖（p=0.0118）和 NO 释放（p=0.01）。DFP 还明显增强 T 辅助（TH）细胞 1 特异性干扰素-γ（IFNG）、白细胞介素 12（IL12）、T 盒转录因子 21（TBX21）和信号转导和转录激活因子 1（STAT1）基因的表达。DFP 通过降低 TH2 网络特异性 GATA3 和白细胞介素 4（IL4）基因的表达水平，同时增加 TH1 网络特异性 IFNG、IL12、TBX21 和 STAT1 基因的表达水平，显著增加肿瘤保护免疫。
DFP 增加了 TH1 特异性网络基因的表达水平，这反过来有助于引发肿瘤保护免疫。
