Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.
BMC Complement Med Ther. 2022 May 23;22(1):145. doi: 10.1186/s12906-022-03625-x.
Use of natural products has been proposed as an efficient method in modulation of immune system and treatment of cancers. The aim of this study was to investigate the potential of cryptotanshinone (CPT), naringenin, and their combination in modulating the immune response towards Th1 cells and the involvement of JAK2/STAT3 signaling pathway in these effects.
Mouse models of delayed type hypersensitivity (DTH) were produced and treated with naringenin and CPT. The proliferation of spleen cells were assessed by Bromodeoxyuridine (BrdU) assay. Flowcytometry and enzyme-linked immunosorbent assay (ELISA) tests were employed to evaluate subpopulation of T-lymphocytes and the levels of cytokines, respectively. The JAK/STAT signaling pathway was analyzed by Western blotting.
We showed higher DTH, increased lymphocyte proliferation, decreased tumor growth and reduced JAK2/STAT3 phosphorylation in mice treated with naringenin and CPT. Moreover, a significant decline in the production of IL-4 and an upsurge in the production of IFN-γ by splenocytes were observed. Additionally, the population of intra-tumor CD4CD25Foxp3 T cells was significantly lower in naringenin + CPT treated animals than that in controls.
Naringenin-CPT combination could exert immunomodulatory effects, suggesting this combination as a novel complementary therapeutic regimen for breast cancer.
利用天然产物已被提议作为调节免疫系统和治疗癌症的有效方法。本研究旨在探讨隐丹参酮（CPT）、柚皮素及其组合在调节 Th1 细胞免疫反应中的潜力，以及 JAK2/STAT3 信号通路在这些作用中的参与。
采用迟发型超敏反应（DTH）小鼠模型，并用柚皮素和 CPT 进行治疗。通过溴脱氧尿苷（BrdU）测定法评估脾细胞的增殖。采用流式细胞术和酶联免疫吸附试验（ELISA）分别评估 T 淋巴细胞亚群和细胞因子水平。通过 Western blot 分析 JAK/STAT 信号通路。
我们发现，用柚皮素和 CPT 治疗的小鼠 DTH 更高，淋巴细胞增殖增加，肿瘤生长减少，JAK2/STAT3 磷酸化减少。此外，脾细胞产生的 IL-4 减少，IFN-γ 增加。此外，与对照组相比，柚皮素+CPT 治疗组肿瘤内 CD4+CD25+Foxp3+T 细胞的数量明显减少。
柚皮素-CPT 联合应用可发挥免疫调节作用，提示该联合应用可能成为乳腺癌的一种新的互补治疗方案。
