Am J Transl Res. 2009 Jan 1;1(1):80-6.
Prostate cancer (PCa), like most human cancers, features dysregulated CD44 expression. Expression of CD44 standard (CD44s), present in benign epithelium, is lost in PCa while pro-invasive splice variant isoform CD44v7-10 is overexpressed. The role of CD44 in silibinin's anti-growth effects was uncertain. To assess silibinin's effects on CD44 promoter activity, PC-3M PCa cells were transfected with luciferase-CD44 promoter construct 24 h prior to 25-200 muM silibinin treatment for 48 h. Also, cells' expression of CD44 RNA (by qRT-PCR) and protein (Western blot analysis) was studied. Silibinin was further tested preoperatively on a pilot cohort of 6 men with PCa compared with 7 matched placebo-treated men, with immunostaining for CD44v7-10 in their prostates. In PC-3M cells, silibinin dose-dependently inhibited CD44 promoter activity up to 87%, caused a 90% inhibition of total CD44 and 70% decrease in CD44v7-10 RNA, and at the protein level, decreased total CD44 at 100-200 muM dose and decreased CD44v7-10 after 3 days. Silibinin decreased adhesion to hyaluronan and fibronectin. Silibinin at 100-200 muM inhibited Egr-1, a regulator of CD44 promoter activity. Men treated with silibinin did not differ in tissue CD44v7-10 expression. In conclusion, CD44 inhibition is one mechanism by which silibinin reduces PCa tumorigenicity.
前列腺癌 (PCa) 与大多数人类癌症一样，其特征是 CD44 表达失调。在 PCa 中，良性上皮细胞中存在的 CD44 标准型 (CD44s) 的表达丢失，而侵袭前剪接变体异构体 CD44v7-10 则过表达。CD44 在水飞蓟宾的抗生长作用中的作用尚不确定。为了评估水飞蓟宾对 CD44 启动子活性的影响，将 PC-3M PCa 细胞用荧光素酶-CD44 启动子构建体转染 24 小时，然后用 25-200 μM 水飞蓟宾处理 48 小时。还研究了细胞中 CD44 RNA（通过 qRT-PCR）和蛋白（Western blot 分析）的表达。在与 7 名匹配的安慰剂治疗男性相比，对 6 名患有 PCa 的男性进行了术前水飞蓟宾测试，对他们的前列腺进行了 CD44v7-10 的免疫染色。在 PC-3M 细胞中，水飞蓟宾呈剂量依赖性地抑制 CD44 启动子活性高达 87%，总 CD44 抑制 90%，CD44v7-10 RNA 减少 70%，在蛋白水平上，在 100-200 μM 剂量下总 CD44 减少，3 天后 CD44v7-10 减少。水飞蓟宾降低了对透明质酸和纤维连接蛋白的粘附性。水飞蓟宾在 100-200 μM 时抑制了 Egr-1，Egr-1 是 CD44 启动子活性的调节剂。用水飞蓟宾治疗的男性在组织 CD44v7-10 表达方面没有差异。总之，CD44 抑制是水飞蓟宾降低 PCa 致瘤性的一种机制。
