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蟾毒灵和华蟾毒精对雄激素依赖性和非依赖性前列腺癌细胞增殖的影响。

Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells.

作者信息

Yeh Jiun-Yih, Huang William J, Kan Shu-Fen, Wang Paulus S

机构信息

Department and Graduate Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.

出版信息

Prostate. 2003 Feb 1;54(2):112-24. doi: 10.1002/pros.10172.

Abstract

BACKGROUND

Cardiac glycosides may induce oncolytic effects in cancers. This study was to evaluate bufalin and cinobufagin effects on the proliferation of prostate cancer cell lines named LNCaP, DU145, and PC3.

METHODS

Cell proliferation was measured by MTT assay. The cytotoxic effects were determined by lactate dehydrogenase measurements. The intracellular calcium concentration (Ca(2+)) was measured by a dual-wavelength spectrometer system. TUNEL assay and flow cytometry were performed to measure percentage of apoptotic cells. A colorimetric assay was to measure caspases activities.

RESULTS

Bufalin and cinobufagin inhibited proliferation of cancer cells at doses of 0.1, 1, or 10 microM after 2-4 days of culture. Cytotoxicity of bufalin and cinobufagin on the DU145 and LNCaP cells was dose-dependent. Bufalin or cinobufagin increased Ca(2+) and apoptosis in cancer cells after a 24-hr culture as well as caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP cells.

CONCLUSIONS

Bufalin and cinobufagin may inhibit the proliferation of prostate cancer cell lines associated with sustained elevation of the Ca(2+) and that of apoptosis.

摘要

背景

强心苷可能在癌症中诱导溶瘤作用。本研究旨在评估蟾毒灵和华蟾酥毒基对前列腺癌细胞系LNCaP、DU145和PC3增殖的影响。

方法

通过MTT法检测细胞增殖。通过乳酸脱氢酶检测确定细胞毒性作用。用双波长光谱仪系统测量细胞内钙浓度(Ca(2+))。进行TUNEL检测和流式细胞术以测量凋亡细胞百分比。采用比色法检测半胱天冬酶活性。

结果

培养2 - 4天后,蟾毒灵和华蟾酥毒基在0.1、1或10微摩尔剂量下抑制癌细胞增殖。蟾毒灵和华蟾酥毒基对DU145和LNCaP细胞的细胞毒性呈剂量依赖性。培养24小时后,蟾毒灵或华蟾酥毒基增加癌细胞内的Ca(2+)和凋亡,以及DU145和PC3细胞中的半胱天冬酶3活性和LNCaP细胞中的半胱天冬酶9活性。

结论

蟾毒灵和华蟾酥毒基可能通过持续升高Ca(2+)和诱导凋亡来抑制前列腺癌细胞系的增殖。

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