Triptolide inhibits the growth and metastasis of solid tumors.
Triptolide inhibits the growth and metastasis of solid tumors.
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DOI：
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发表时间：
2003
影响因子：
5.7
通讯作者：
Shanmin Yang;Jinguo Chen;Zhen Guo;Xue-ming Xu;Luping Wang;X. Pei;Jing Yang;C. Underhill;
中科院分区：
文献类型：
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作者：
Shanmin Yang;Jinguo Chen;Zhen Guo;Xue-ming Xu;Luping Wang;X. Pei;Jing Yang;C. Underhill;
雷公藤甲素(TPL)是从中草药雷公藤(Tripterygium Wilfordii Hook F)中提纯的一种二萜类三环氧化物，在多个模型体系中进行了抗肿瘤活性测试。在体外，TPL在极低浓度(2~10 ng/ml)下抑制肿瘤细胞的增殖和集落形成，且作用强于紫杉醇。同样，在体内，TPL治疗小鼠2-3周抑制了由四种不同肿瘤细胞系(B16黑色素瘤、MDA-435乳腺癌、TSU膀胱癌和MGC80-3胃癌)形成的异种移植瘤的生长，表明TPL对含有野生型和突变型P53的肿瘤具有广泛的活性。此外，TPL还能抑制B16F10细胞对小鼠肺和脾的实验性转移。TPL的抗肿瘤作用与阿霉素、丝裂霉素、顺铂等常规抗肿瘤药物相当或更好。重要的是，由于多药耐药基因1的过度表达而对紫杉醇产生耐药性的肿瘤细胞仍然对TPL的作用敏感。对培养的肿瘤细胞的研究表明，TPL诱导了细胞凋亡，并减少了几种调节细胞周期的分子的表达。综上所述，这些结果表明TPL作为一种新的抗肿瘤药物具有几个吸引人的特征。
Triptolide (TPL), a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F, was tested for its antitumor properties in several model systems. In vitro, TPL inhibited the proliferation and colony formation of tumor cells at extremely low concentrations (2-10 ng/ml) and was more potent than Taxol. Likewise, in vivo, treatment of mice with TPL for 2-3 weeks inhibited the growth of xenografts formed by four different tumor cell lines (B16 melanoma, MDA-435 breast cancer, TSU bladder cancer, and MGC80-3 gastric carcinoma), indicating that TPL has a broad spectrum of activity against tumors that contain both wild-type and mutant forms of p53. In addition, TPL inhibited experimental metastasis of B16F10 cells to the lungs and spleens of mice. The antitumor effect of TPL was comparable or superior with that of conventional antitumor drugs, such as Adriamycin, mitomycin, and cisplatin. Importantly, tumor cells that were resistant to Taxol attributable to the overexpression of the multidrug resistant gene 1 were still sensitive to the effects of TPL. Studies on cultured tumor cells revealed that TPL induced apoptosis and reduced the expression of several molecules that regulate the cell cycle. Taken together, these results suggest that TPL has several attractive features as a new antitumor agent.