Sanguinarine inhibits the proliferation of BGC-823 gastric cancer cells via regulating miR-96-5p/miR-29c-3p and the MAPK/JNK signaling pathway.

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.

[Effect of Dingzhi Xiaowan on miR-16 expression and 5-HT reuptake].

This study is to investigate the effect of antidepressant medicine prescription Dingzhi Xiaowan (DZ) on miR-16 expression levels in vitro and in vivo, and to explore the mechanism of DZ elevated levels of 5-HT from the perspective of post transcriptional regulation. Firstly, a chronic unpredictable mild moderate stimulation (CUMS) combined with solitary rising depression rat model was established, the behavior changes were detected after different doses of DZ (600, 300, 150 mg·kg⁻¹) given for 3 weeks, high performance liquid chromatography (HPLC) was used to detect 5-HT level in hippocampal, PCR method was used to observe the effect of DZ on the expression of SERT mRNA and miR-16 in hippocampus of CUMS rat. The effects of DZ (10, 100, 200, 500 mg·L⁻¹) on the expression of miR-16 and SERT mRNA in the cell model induced by miR-16 silencing and corticosterone or glutamate injury were observed in primary cultured hippocampal neurons of rats in vitro. It was found that 300 mg·kg⁻¹ and 600 mg·kg⁻¹ DZ could significantly improve the behavioral score of CUMS rats, increase the level of 5-HT in hippocampus, and increase the expression of miR-16 and decrease the expression of SERT in the hippocampus of rats. At the same time, in primary cultured hippocampal neurons, 100, 200, 500 mg·L⁻¹ of DZ could significantly increase the expression level of miR-16 in miR-16 silencing and corticosterone or glutamate injury cell model, and decrease the expression level of SERT significantly. So DZ could inhibit the reuptake of 5-HT by inhibiting the expression of SERT by up regulating the expression level of miR-16, and finally increase the level of 5-HT in the brain and exert antidepressant effect.