Department of Endocrinology,The First Hospital of Lanzhou University, No. 1 West Donggang Road, Lanzhou, Gansu，730000, China; The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, China.
Department of Endocrinology,The First Hospital of Lanzhou University, No. 1 West Donggang Road, Lanzhou, Gansu，730000, China.
Biomed Pharmacother. 2020 Aug;128:110327. doi: 10.1016/j.biopha.2020.110327. Epub 2020 Jun 4.
Matrine is a natural product extracted from the root of Sophora flavescens that has been shown to be a promising alternative drug in different types of cancer. Here, we aimed to investigate the antitumor effects of matrine on human papillary thyroid cancer (PTC) and explore the underlying molecular mechanisms. Our data demonstrated the following findings. (a) The expression of miR-182-5p was significantly upregulated in PTC tissues and cell lines. (b) Matrine inhibited the expression of miR-182-5p and induced the apoptosis of TCP-1 and BCPAP cells in a dose-dependent manner. (c) Matrine increased caspase3 expression levels and reduced Bcl-2 expression levels in both TCP-1 and BCPAP cells. (d) Matrine appreciably inhibited PTC tumor growth in vivo. (e) After miR-182-5p overexpression, matrine-induced apoptosis and caspase3 activation were inhibited, and the matrine-induced decrease in Bcl-2 expression was abolished. (f) Overexpression of miR-182-5p counteracted the inhibitory effects of matrine on PTC tumor growth. In conclusion, these results demonstrate that matrine exerts antitumor effects possibly by inducing the apoptosis of TCP-1 and BCPAP cells, decreasing the level of Bcl-2, activating caspase3 and suppressing PTC tumor growth by downregulating the expression of miR-182-5p. These findings explain the anticancer mechanisms of matrine in PTC and identify miR-182-5p as an effective target of matrine in PTC treatment.
苦参碱是从苦参根中提取的天然产物，已被证明是多种癌症有前途的替代药物。在这里，我们旨在研究苦参碱对人甲状腺乳头状癌（PTC）的抗肿瘤作用，并探讨其潜在的分子机制。我们的数据表明了以下发现。（a）miR-182-5p 的表达在 PTC 组织和细胞系中明显上调。（b）苦参碱以剂量依赖的方式抑制 miR-182-5p 的表达并诱导 TCP-1 和 BCPAP 细胞凋亡。（c）苦参碱增加了 caspase3 表达水平，并降低了 TCP-1 和 BCPAP 细胞中 Bcl-2 的表达水平。（d）苦参碱在体内显著抑制 PTC 肿瘤生长。（e）miR-182-5p 过表达后，苦参碱诱导的细胞凋亡和 caspase3 激活受到抑制，苦参碱诱导的 Bcl-2 表达降低被消除。（f）miR-182-5p 的过表达抵消了苦参碱对 PTC 肿瘤生长的抑制作用。总之，这些结果表明苦参碱通过诱导 TCP-1 和 BCPAP 细胞凋亡、降低 Bcl-2 水平、激活 caspase3 以及下调 miR-182-5p 的表达来抑制 PTC 肿瘤生长，从而发挥抗肿瘤作用。这些发现解释了苦参碱在 PTC 中的抗癌机制，并确定 miR-182-5p 是苦参碱在 PTC 治疗中的有效靶点。
