Department of Pharmacy, Xuanwu Hospital of Capital Medical University, 45 Changchun Road, Xicheng District, 100053, Beijing, China.
Department of Pharmacy, Chinese PLA General Hospital, 100853, Beijing, China.
J Nat Med. 2019 Sep;73(4):777-788. doi: 10.1007/s11418-019-01330-7. Epub 2019 Jun 26.
Sanguinarine (SAN), a quaternary benzophenanthridine alkaloid extracted from the root of Papaveraceae plants, has shown antitumour effects in multiple cancer cells. However, the therapeutic effects and the underlying mechanisms of SAN in gastric cancer (GC) remain elusive. In this study, the in vitro proliferation inhibition effect of SAN in GC cells was determined using CCK-8 assay, the in vivo antitumor effect of SAN was evaluated in mice with xenotransplanted tumor. The mechanism underlying the antitumor activity of SAN was explored by gene microarray assay and bioinformatics analysis. The levels of differentially expressed miRNAs and target genes were verified by real-time RT-PCR and immunohistochemistry. SAN inhibited the proliferation of BGC-823 cells in a concentration-dependent manner in vitro and in vivo. The miR-96-5p and miR-29c-3p were significantly upregulated in untreated BGC-823 cells and significantly downregulated in SAN treated cells. The mRNA and protein expression of their target gene MAP4K4 were upregulated in SAN treated xenotransplanted tumors, and pMEK4 and pJNK1 proteins in the MAPK/JNK signaling pathway were also upregulated by SAN. These indicate that SAN may inhibit the proliferation of BGC-823 cells through the inhibition of miR-96-5p and miR-29c-3p expression, and subsequent activation of the MAPK/JNK signaling pathway.
血根碱（SAN）是从罂粟科植物根部提取的一种季铵苯并菲啶生物碱，已在多种癌细胞中显示出抗肿瘤作用。然而，SAN 治疗胃癌（GC）的疗效和作用机制仍不清楚。在这项研究中，通过 CCK-8 测定法确定了 SAN 在 GC 细胞中的体外增殖抑制作用，在异种移植肿瘤小鼠中评估了 SAN 的体内抗肿瘤作用。通过基因微阵列分析和生物信息学分析探讨了 SAN 抗肿瘤活性的作用机制。通过实时 RT-PCR 和免疫组织化学验证了差异表达 miRNA 和靶基因的水平。SAN 体外和体内均呈浓度依赖性抑制 BGC-823 细胞的增殖。miR-96-5p 和 miR-29c-3p 在未经处理的 BGC-823 细胞中显着上调，在 SAN 处理的细胞中显着下调。MAP4K4 的靶基因的 mRNA 和蛋白表达在 SAN 处理的异种移植肿瘤中上调，MAPK/JNK 信号通路中的 pMEK4 和 pJNK1 蛋白也被 SAN 上调。这表明 SAN 可能通过抑制 miR-96-5p 和 miR-29c-3p 的表达，随后激活 MAPK/JNK 信号通路，抑制 BGC-823 细胞的增殖。
