Li Xiangnan, Chen Wenna, Miao Lanying, Sun Hongwei, Gao Xia, Guo Shengnan, Zhang Yueshi, Yang Yufeng, Guo Junfu
Teaching and Experiment Center, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning, China.
Department of Medical Laboratory Science, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning, China.
Evid Based Complement Alternat Med. 2022 Jul 14;2022:4675815. doi: 10.1155/2022/4675815. eCollection 2022.
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 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. 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 by upregulating CMTM2 expression.
四君子汤（SJZ）是一种中药配方，临床上用于对抗多种恶性肿瘤，包括胃癌（GC）。在先前的研究中，我们已经表明SJZ在SGC7901细胞异种移植小鼠模型中发挥抗癌作用。然而，其潜在机制尚不清楚。本研究的目的是评估SJZ对GC细胞增殖、迁移、侵袭和癌症干细胞样特性的影响及机制。进行高通量mRNA测序分析以研究异种移植肿瘤中基因表达的整体变化，在SJZ组和模型组之间总共鉴定出56个显著差异表达基因（43个上调基因和13个下调基因）。我们将SJZ干预后显著增加的CMTM2作为SJZ的候选靶基因进行研究。结果表明，CMTM2在SJZ处理的SGC7901细胞中表达升高，敲低其表达部分阻碍了SJZ对GC细胞增殖、迁移和侵袭的抑制作用。此外，SJZ处理抑制了GC细胞的球体形成和集落形成能力，同时伴随着包括SOX2、NANOG和CD44在内的干细胞标志物的下调。敲低拮抗了SJZ对SGC7901细胞癌症干细胞样特性的影响。因此，SJZ通过上调CMTM2表达有效抑制了GC细胞的增殖、迁移、侵袭和癌症干细胞样特性。
