Wang Bo, Jiang Jianping, Zhang Yun, Shen Yingying, Wu Liqiang, Tang Siqi, Lin Shengyun
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Preparation Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Exp Ther Med. 2021 May;21(5):503. doi: 10.3892/etm.2021.9934. Epub 2021 Mar 17.
Treatment for higher-risk patients with myelodysplastic syndrome (MDS) should aim to modify the disease course by avoiding progression to acute myeloid leukemia and improving survival. When a patient is not eligible for intensive chemotherapy and lacks a donor hematopoietic cell source, or for a patient in a poor economic situation, consideration can be given to the use of Chinese herbal medicine. Numerous plant extracts, such as camptothecin, vinblastine and paclitaxel, have been reported to display antitumor effects, serving as potential therapeutic strategies for cancer. In the present study, the ultra-performance liquid chromatography-tandem mass spectrometry system (Waters Corporation) was used to detect the main chemical components of HDE, CCK-8 assay to detect the effects of HDE and BIIB021 on the proliferation of SKM-1 cells; and designed hTERT-small interfering (si)RNAs to detect the effects of HDE and BIIB021 on SKM-1 cell apoptosis after HTERT gene knockdown. The present study investigated a newly extracted coumarin HDE, the active component in Willd, which efficiently inhibited SKM-1 (MDS cell line) proliferation and induced apoptosis, as determined by performing Cell Counting Kit-8 and flow cytometry assays, respectively. The effect of HDE was associated with decreased telomerase activity. Moreover, heat shock protein 90 inhibitor BIIB021 significantly enhanced the antitumor effects of HDE on SKM-1 cells. In addition, SKM-1 cell apoptosis was increased in human telomerase reverse transcriptase (hTERT)-knockdown cells compared with the negative control group. Cell apoptosis in hTERT-knockdown SKM-1 cells was further enhanced following HDE, BIIB021 or combination treatment, as evidenced by increased levels of cleaved caspase 3, cleaved caspase 8 and cleaved poly ADP ribose polymerase. Collectively, the results indicated synergistic antitumor effects of HDE and BIIB021, providing a novel therapeutic combination for higher-risk MDS.
对于高危骨髓增生异常综合征（MDS）患者的治疗，应旨在通过避免进展为急性髓系白血病和提高生存率来改变疾病进程。当患者不符合强化化疗条件且缺乏供体造血细胞来源时，或者对于经济状况较差的患者，可以考虑使用中药。据报道，许多植物提取物，如喜树碱、长春碱和紫杉醇，具有抗肿瘤作用，可作为癌症的潜在治疗策略。在本研究中，使用超高效液相色谱-串联质谱系统（沃特世公司）检测HDE的主要化学成分，采用CCK-8法检测HDE和BIIB021对SKM-1细胞增殖的影响；设计hTERT小干扰（si）RNA，检测HDE和BIIB021对HTERT基因敲低后SKM-1细胞凋亡的影响。本研究调查了一种新提取的香豆素HDE，它是Willd中的活性成分，通过分别进行细胞计数试剂盒-8和流式细胞术检测，发现其能有效抑制SKM-1（MDS细胞系）增殖并诱导凋亡。HDE的作用与端粒酶活性降低有关。此外，热休克蛋白90抑制剂BIIB021显著增强了HDE对SKM-1细胞的抗肿瘤作用。此外，与阴性对照组相比，人端粒酶逆转录酶（hTERT）敲低细胞中的SKM-1细胞凋亡增加。HDE、BIIB021或联合处理后，hTERT敲低的SKM-1细胞中的细胞凋亡进一步增强，这通过裂解的半胱天冬酶3、裂解的半胱天冬酶8和裂解的聚ADP核糖聚合酶水平升高得以证明。总体而言，结果表明HDE和BIIB021具有协同抗肿瘤作用，为高危MDS提供了一种新的治疗组合。
