Ma Yicong, Feng Cuiling, Wang Jingjing, Chen Ziwei, Wei Peng, Fan Angran, Wang Xu, Yu Xue, Ge Dongyu, Xie Hua, Liu Li, Zhang Qian, Li Xu-Hui
Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.
Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, Zhejiang 314006, P.R. China.
Oncol Lett. 2019 Mar;17(3):3503-3510. doi: 10.3892/ol.2019.9946. Epub 2019 Jan 18.
Hepatocellular carcinoma (HCC) is a serious threat to human health. Chemotherapy drugs such as cisplatin are widely used in cancer treatment, but can cause severe side effects. Hydroxyl safflower yellow A (HSYA) is a water-soluble chalcone glycoside substance extracted from safflowers (Carthamus tinctorius L.) that has been reported to inhibit tumor growth with few side effects. The tumor immune microenvironment is crucial for the proliferation and invasiveness of tumor cells, and it is mediated by forkhead box P3-positive (FOXP3+) regulatory T cells (Tregs) and retinoic acid receptor-related orphan receptor-γ (RORγ)-expressing Th17 cells. FOXP3+ Tregs inhibit immunoreaction and FOXP3 is a key indicator of Tregs. RORγ isoform 2, also known as RORγt, is an important transcription factor in Th17 cells that may promote cancer progression. In the present study, the antitumor effect of HSYA on HCC was investigated, as well as its impact on the tumor immune microenvironment. Following the establishment of a mouse model for HCC, hematoxylin and eosin staining were performed to observe histological changes in liver tumors, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. The proportion of FOXP3+ Tregs in the spleen was determined by flow cytometry, and expression levels of Foxp3 and Rorγt were examined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study showed that cisplatin inhibited tumor growth, caused weight loss and reduced the immunoreactivity of the mice. HSYA inhibited tumor growth without causing significant weight loss. The proportion of FOXP3-expressing Tregs in the spleen and the expression of Foxp3 and Rorγt mRNA decreased following treatment with certain doses of HSYA. In conclusion, HSYA inhibited tumor growth without detrimental effects on the weight of the mice, indicating that HSYA may be suitable as a novel therapy for HCC patients.
肝细胞癌（HCC）对人类健康构成严重威胁。顺铂等化疗药物广泛应用于癌症治疗，但会引起严重的副作用。羟基红花黄色素A（HSYA）是从红花（Carthamus tinctorius L.）中提取的一种水溶性查尔酮糖苷物质，据报道其能抑制肿瘤生长且副作用较少。肿瘤免疫微环境对肿瘤细胞的增殖和侵袭至关重要，它由叉头框P3阳性（FOXP3+）调节性T细胞（Tregs）和表达视黄酸受体相关孤儿受体-γ（RORγ）的Th17细胞介导。FOXP3+ Tregs抑制免疫反应，FOXP3是Tregs的关键指标。RORγ亚型2，也称为RORγt，是Th17细胞中的一种重要转录因子，可能促进癌症进展。在本研究中，研究了HSYA对HCC的抗肿瘤作用及其对肿瘤免疫微环境的影响。建立HCC小鼠模型后，进行苏木精-伊红染色以观察肝肿瘤的组织学变化，并称量脾脏和胸腺重量以计算脾脏和胸腺指数。通过流式细胞术测定脾脏中FOXP3+ Tregs的比例，并通过逆转录-定量聚合酶链反应和蛋白质印迹分析检测Foxp3和Rorγt的表达水平。本研究结果表明，顺铂抑制肿瘤生长，导致体重减轻并降低小鼠的免疫反应性。HSYA抑制肿瘤生长但未引起明显体重减轻。用一定剂量的HSYA处理后，脾脏中表达FOXP3的Tregs比例以及Foxp3和Rorγt mRNA的表达下降。总之，HSYA抑制肿瘤生长且对小鼠体重无有害影响，表明HSYA可能适合作为HCC患者的一种新疗法。
