Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Traditional Chinese Medicine, Guangdong Geriatric Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Integr Cancer Ther. 2024 Jan-Dec;23:15347354241263018. doi: 10.1177/15347354241263018.
The Chinese medicine Jianpi-Huayu decoction (, JPHY) can alleviate cancer-related fatigue in patients with liver cancer. However, its mechanism remains unclear. In this study, we used BALB/c mice with liver cancer model to investigate whether JPHY alleviates cancer-related fatigue by regulating Th1/Th2 immune balance; and the possible association with the IL-27/STAT1 signaling pathway. We established a mouse model of liver cancer fatigue. Mice were gavaged with physiological saline, low, medium, or high concentrations of JPHY respectively; and intraperitoneal injection of fludarabine (STAT1 pathway inhibitor) with JPHY for 21 days. We recorded the general condition of the mice, and assessed fatigue using scoring criteria and Exhausted Swimming Test. We calculated the spleen and thymus indices, performed H&E staining and immunohistochemical analysis on liver tumor tissues to observe the tumor proliferation marker ki67. We quantified the secretion levels of IFN-γ and IL-2 produced by Th1 cells in serum and splenic lymphocytes, as well as the secretion of IL-4, IL-10 by Th2 cells, and IL-27 in the signaling pathway through ELISA analysis. We evaluated the expression levels of p-STAT1 and STAT1 in spleen tissues using Western blot analysis. JPHY exhibits a therapeutic effect on hepatocellular carcinoma-induced splenomegaly in murine models by upregulating the pro-inflammatory cytokines IFN-γ and IL-2 and downregulating the anti-inflammatory cytokines IL-4 and IL-10. Moreover, JPHY suppresses ki67 expression, reduces tumor-related inflammation infiltration, and ameliorates cancer-associated fatigue. Additionally, the expression of phosphorylated protein p-STAT1 is down-regulated. JPHY may improve the Th1/Th2 immune balance through its anti-inflammatory effects and promotion of IL-27-induced STAT1 phosphorylation, thereby alleviating fatigue in mice with liver cancer.
中药健脾化瘀汤（JPHY）可减轻肝癌患者的癌因性疲乏。然而，其作用机制尚不清楚。本研究采用 BALB/c 肝癌模型小鼠，探讨 JPHY 是否通过调节 Th1/Th2 免疫平衡缓解癌因性疲劳，及其与 IL-27/STAT1 信号通路的可能关联。
我们建立了肝癌疲劳小鼠模型。分别用生理盐水、低、中、高浓度 JPHY 灌胃，并用 JPHY 联合氟达拉滨（STAT1 通路抑制剂）腹腔注射 21 天。记录小鼠一般情况，疲劳评分标准和衰竭游泳试验评估疲劳程度。计算脾、胸腺指数，对肝肿瘤组织行 H&E 染色和免疫组化分析，观察肿瘤增殖标志物 ki67。酶联免疫吸附试验（ELISA）分析检测血清和脾淋巴细胞中 Th1 细胞产生的 IFN-γ 和 IL-2 以及 Th2 细胞分泌的 IL-4、IL-10 以及信号通路中 IL-27 的分泌水平。Western blot 分析评估脾组织中 p-STAT1 和 STAT1 的表达水平。
JPHY 通过上调促炎细胞因子 IFN-γ 和 IL-2，下调抗炎细胞因子 IL-4 和 IL-10，对肝癌诱导的荷瘤小鼠脾肿大具有治疗作用。此外，JPHY 抑制 ki67 表达，减少肿瘤相关炎症浸润，改善癌因性疲劳。此外，磷酸化蛋白 p-STAT1 的表达下调。
JPHY 可能通过其抗炎作用和促进 IL-27 诱导的 STAT1 磷酸化，改善肝癌小鼠的 Th1/Th2 免疫平衡，从而缓解疲劳。
