25-methoxyl-dammarane-3 beta, 12 beta, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression
25-methoxyl-dammarane-3 beta, 12 beta, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression
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25-甲氧基-达玛烷-3β、12β、20-三醇和青蒿素通过下调睾丸特异性蛋白酶 50 (TSP50) 表达协同抑制 MDA-MB-231 细胞增殖
DOI：
10.1007/s13277-016-5037-7
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Li Yuxin
中科院分区：
文献类型：
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作者：
Wang Danfeng;Zhao Yuqing;Wang Yimeng;Rong Yan;Qin Hongshuang;Bao Yongli;Song Zhenbo;Yu Chunlei;Sun Luguo;Li Yuxin
虽然癌症的发病率持续增加，但目前的治疗方案仍不完善。因此，迫切需要发现新的靶向抗癌疗法。睾丸特异性蛋白酶50（Testes-specific protease 50，TSP 50）在大多数肿瘤组织中异常表达，下调TSP 50的表达可抑制细胞增殖，诱导细胞凋亡，使其成为肿瘤治疗的潜在靶点。本研究构建了萤火虫荧光素酶报告基因pGL 3-TSP 50 -3′-UTR作为药物筛选模型，筛选出靶向TSP 50 mRNA的潜在候选化合物。我们鉴定了由70%的25-甲基-达玛烷-3 β，12β，20-三醇和30%的青蒿素组成的化合物7 P3 A，其能够抑制TSP 50 -3′-UTR报告基因活性以及TSP 50的表达。进一步研究发现，7 P3 A可抑制MDA-MB-231细胞增殖，诱导细胞周期阻滞，过表达TSP 50可部分逆转7 P3 A的作用。体内研究表明，7 P3 A可以抑制乳腺癌异种移植模型中的肿瘤生长。这些结果表明，7 P3 A表现出抗癌作用，部分通过下调TSP 50表达。
While the incidence of cancer continues to increase, the current therapeutic options remain imperfect. Therefore, there is an urgent need to discover new targeted anti-cancer therapies. Testes-specific protease 50 (TSP50) is abnormally expressed in most cancer tissues and downregulation of TSP50 expression can reduce cell proliferation and induce cell apoptosis, which makes it a potential target for cancer therapy. In this study, we constructed a firefly luciferase reporter pGL3-TSP50-3′-UTR as a drug screening model to screen potential candidate compounds that target TSP50 mRNA. We identified the compound 7P3A, which consists of 70 % 25-methoxyl-dammarane-3β, 12β, 20-triol and 30 % artemisinin, as being capable of inhibiting the TSP50-3′-UTR reporter activity, as well as the expression of TSP50. Further investigation revealed that 7P3A could inhibit MDA-MB-231 cell proliferation and induce cell cycle arrest, and over-expression of TSP50 partially reversed the effect of 7P3A. In vivo investigation showed that 7P3A could inhibit tumor growth in a xenograft model of breast cancer. These results suggest that 7P3A exhibits anti-cancer effects, in part, through downregulation of TSP50 expression.