| 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. |
| Induction of apoptosis in renal cell carcinoma by cinobufotalin through inhibition of Notch1 signal activation |
| Received:September 29, 2019 Revised:June 19, 2020 |
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| KeyWord:renal cell carcinoma; cinobufotalin; cell line 769-P |
| 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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| Abstract: |
| 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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