| qing li,Xing Huang. Induction of apoptosis in renal cell carcinoma by cinobufotalin through inhibition of Notch1 signal activation. Oncol Transl Med, 2020, 6: 217-221. |
| 华蟾素通过抑制Notch1信号活化诱导肾癌细胞凋亡的实验研究* |
| Induction of apoptosis in renal cell carcinoma by cinobufotalin through inhibition of Notch1 signal activation |
| Received:September 29, 2019 Revised:June 19, 2020 |
| DOI：10.1007/s10330-019-0382-2 |
| 中文关键词: 肾细胞癌；华蟾素；细胞系769-P |
| 英文关键词: renal cell carcinoma; cinobufotalin; cell line 769-P |
| 基金项目:2015年江苏省卫生计生委科研课题（H201516） |
| Author Name | Affiliation | E-mail | | qing li* | Department of Nephrology, Jiangsu Health and Health Vocational College | poweihuangjg@163.com | | Xing Huang | Affiliated Hospital of Nantong University, Nantong 226021, China | |
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| 中文摘要: |
| 目的：探讨华蟾素诱导肾癌细胞凋亡的作用及可能的机制。方法：收集64例肾癌患者为研究对象，采用免疫组化法检测肾癌组织、癌旁组织及正常组织中Notch1的表达率，统计分析Notch1表达对患者临床病理特征的影响。采用0mg/L、10mg/L、20mg/L、40mg/L华蟾素处理人肾癌细胞系769-P，检测各组肾癌细胞的增殖活性及凋亡率。采用RT-PCR法及Western-blot检测Notch1、Bcl-2、Pro-caspase3的表达水平。结果：（1）Notch1在肾癌、癌旁组织、正常组织中的阳性率分别为75.0%（48/64）、45.3%（29/64）、9.4%（6/64），差异具有统计学意义（P＜0.05）。Notch1表达对肾癌患者TNM分期、Fuhrman分级、肿瘤大小有明显影响（P＜0.05）。（2）华蟾素以浓度0、10mg/L、20mg/L、40mg/L干预769-P细胞后，24h时的细胞抑制率分别为0、6.85%、11.37%、16.33%，48h时为0、13.57%、20.14%、31.69%，72h时为0、19.97%、28.53%、51.42%。华蟾素对769-P细胞的生长抑制作用呈明显的剂量依赖性和时间依赖性。同时，在24h时，769-P细胞的凋亡率分别为（8.2±3.1）%、（19.8±5.6）%、（33.7±5.0）%、（51.5±6.8）%。华蟾素对促进769-P细胞凋亡的作用呈明显的剂量依赖性。（3）RT-PCR检测发现，随着药物干预浓度的提高，Notch1 mRNA相对表达量明显下降，Bcl-2 mRNA、Pro-caspase3 mRNA呈明显上升趋势。Western-blot检测也得出相同的趋势。结论：华蟾素可通过抑制肾癌细胞生长、诱导肾癌细胞凋亡发挥抗肿瘤作用，这可能与抑制Notch1信号活化有关。 |
| 英文摘要: |
| Objective The aim of this study was to investigate the effect of cinobufotalin on apoptosis in renal cell
carcinoma and its possible mechanism of action.
Methods The expression levels of Notch1 in renal cancer cells, as well as in adjacent and normal tissues
were assessed in 64 patients with renal cellcarcinoma. The 769-P cells were treated with 0, 10, 20 and
40 mg/L cinobufotalin and the proliferation activity and apoptotic rate of the cells were measured. The
expression levels of Notch1, Bcl-2, and Pro-caspase 3 were detected by RT-PCR and Western-blot.
Results (1) The rates of Notch1 expression in renal cancer cells, adjacent tissues, and normal tissues
were 75.0%, 45.3%, and 9.4%, respectively. Notch1 expression had significant effects on tumor, node and
metastasis (TNM) staging, Fuhrman grade, and tumor size in patients with renal cell carcinoma (P < 0.05);
(2) The inhibition rates of cinobufotalin on 769-P cells were 0%, 6.85%, 11.37%, and 16.33% at 24 h; 0%,
13.57%, 20.14%, and 31.69% at 48 h; 0%, 19.97%, 28.53% and 51.42% at 72 h. At 24 h, the apoptotic rates
were 8.2 ± 3.1%, 19.8 ± 5.6%, 33.7 ± 5.0%, and 51.5 ± 6.8%.The effect of cinobufotalin on apoptosis of
769-P cells was dose-dependent; (3) RT-PCR assay showed that protein expression levels for Notch1, Bcl-
2, and Pro-caspase 3 were significantly decreased with the increase of drug concentration. Western-blot
analysis also showed that Notch1, Bcl-2 and Pro-caspase 3 protein levels showed a significant downward
trend with the increase of drug concentration.
Conclusion Cinobufotalin inhibits the growth of renal cancer cells and induces apoptosis in renal cell
carcinoma, which may be related to the inhibition of Notch1 signal activation. |
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