RESUMO
The Si-Jun-Zi decoction (SJZ), a traditional Chinese medicine (TCM) formula, is used clinically against multiple malignancies, including gastric cancer (GC). In previous study, we have shown that SJZ plays an anticancer role in SGC7901 cell xenograft mice models. However, the underlying mechanisms are unclear. The objective of this study was to evaluate the effect and mechanism of SJZ on the proliferation, migration, invasion, and cancer stem cell-like properties of GC cells. High-throughput mRNA sequencing analysis was performed to investigate the global alterations in gene expression in xenograft tumors, and 56 significantly differentially expressed genes (43 upregulated and 13 downregulated genes) were identified between the SJZ group and the Model group totally. We focused on CMTM2, which was significantly increased after SJZ intervention, as a candidate target gene of SJZ. The results indicated that CMTM2 expression was elevated in SJZ-treated SGC7901 cells and knocking-down CMTM2 expression partially hampered the inhibitory effects of SJZ on the proliferation, migration, and invasion of GC cells. Moreover, SJZ treatment repressed the spheroid and colony-forming capacity in GC cells, accompanied by downregulation of stem cell markers including SOX2, NANOG, and CD44. CMTM2 knockdown antagonized the effects of SJZ on the cancer stem cell-like properties of SGC7901 cells. Thus, SJZ effectively suppressed the proliferation, migration, invasion, and cancer stem cell-like properties of GC cells in vitro by upregulating CMTM2 expression.
RESUMO
Objective. The present study aimed to investigate the potential mechanism underlying the antitumor effect of Si Jun Zi Tang (SJZT) decoction on gastric cancer. Methods. Twelve human gastric cancer SGC7901 cell xenograft nude mouse models were established. The mice were randomly divided into the Model group and SJZT group. SJZT exerted significant antitumor effects after 21 days of decoction administration. High-throughput sequencing was used to analyze the microRNA (miRNA) expression profiles of tumor tissues. Bioinformatics analysis was performed to provide further information regarding the differentially expressed miRNAs. Five representative differentially expressed miRNAs and four predicted target genes were further validated using quantitative real-time reverse transcription PCR (qRT-PCR). Results. We identified 33 miRNAs that were differentially expressed in the SJZT group compared with the Model group. Among them, 32 miRNAs were upregulated and 1 miRNA was downregulated. Bioinformatic analysis showed that most of miRNAs acted as tumor suppressors and their target genes participated in multiple signaling pathways, including the PI3K/Akt signaling pathway, microRNAs in cancer, and Wnt signaling pathway. The qRT-PCR result confirmed that miR-223-3p, miR-205-5p, miR-147b-3p, and miR-223-5p were overexpressed and their respective paired target genes FUT9, POU2F1, MUC4, and RAB14 mRNA were obviously downregulated in the SJZT group compared with those in the Model group. Network analysis revealed that miR-223-3p and miR-205-5p shared two targets POU2F1 (encoding POU class 2 homeobox 1) and FUT9 (encoding fucosyltransferase 9), suggesting they have a common role in certain pathways. Conclusion. This study provided novel insights into the anticancer mechanism of SJZT against gastric cancer, which might be partly related to the modulation of miRNA expression and their target pathways in tumors.
