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雷公藤甲素对人乳腺癌干细胞和原发性乳腺癌细胞的体外及体内细胞毒性作用。

Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells.

作者信息

Li Junjie, Liu Ruilei, Yang Ye, Huang Yong, Li Xi, Liu Ruiming, Shen Xiaoyan

机构信息

Department of Breast Surgery, Sichuan Cancer Hospital, Chengdu 610041, P.R. China.

Department of Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.

出版信息

Oncol Rep. 2014 May;31(5):2181-6. doi: 10.3892/or.2014.3115. Epub 2014 Mar 27.

Abstract

We investigated the potential efficacy of the Chinese herbal extract triptolide for the treatment of human breast cancer by measuring the triptolide-induced cytotoxicity in cultures of human primary breast cancer cells (BCCs) and breast cancer stem cells (BCSCs) in vitro and in vivo. Human BCCs and BCSCs from invasive ductal carcinoma samples were cultured and treated with 0.1, 0.5 or 1.0 µM triptolide. Cell death and apoptosis were measured after 24, 48 and 72 h of treatment. Mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. Triptolide was cytotoxic against both human primary BCCs and BCSCs in vitro (P<0.05), but the cytotoxicity was stronger against the BCCs. In response to 1 µM triptolide for 72 h, the apoptotic rates were approximately 60% for BCCs and 30% for BCSCs. The BCSCs exhibited a high formation rate of tumors when implanted subcutaneously in nude BALB/c mice. Triptolide treatment in vivo significantly inhibited tumor growth compared with mock treatment. In conclusion, the cytotoxicity of triptolide against BCCs and BCSCs in vitro and in vivo suggests that this natural diterpenoid triepoxide compound may have clinical applications for the suppression of breast tumor growth.

摘要

我们通过在体外和体内测量雷公藤甲素对人原发性乳腺癌细胞(BCCs)和乳腺癌干细胞(BCSCs)培养物的细胞毒性,研究了中药提取物雷公藤甲素治疗人类乳腺癌的潜在疗效。培养来自浸润性导管癌样本的人BCCs和BCSCs,并用0.1、0.5或1.0 μM雷公藤甲素处理。在处理24、48和72小时后测量细胞死亡和凋亡情况。当皮下植入裸BALB/c小鼠时,发现乳腺球具有高度致瘤性。雷公藤甲素在体外对人原发性BCCs和BCSCs均具有细胞毒性(P<0.05),但对BCCs的细胞毒性更强。在1 μM雷公藤甲素作用72小时后,BCCs的凋亡率约为60%,BCSCs为30%。当皮下植入裸BALB/c小鼠时,BCSCs表现出高肿瘤形成率。与模拟处理相比,体内雷公藤甲素处理显著抑制肿瘤生长。总之,雷公藤甲素在体外和体内对BCCs和BCSCs的细胞毒性表明,这种天然二萜三环氧化物化合物可能在抑制乳腺肿瘤生长方面具有临床应用价值。

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