Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
J Cell Physiol. 2019 Dec;234(12):22207-22219. doi: 10.1002/jcp.28788. Epub 2019 Jun 13.
The metastatic rate of human cutaneous squamous cell carcinoma (CSCC) has increased in recent years. Despite the current advances in therapies, effective treatments remain lacking. Ginsenoside 20(R)-Rg3 is an effective antitumor monomer extracted from ginseng, but the role of Rg3 in CSCC remains unknown. It has been reported that aberrantly elevated histone deacetylase 3 (HDAC3) is involved in tumor malignancy in multiple malignant tumors. However, the effects of HDAC3 on the regulation of c-Jun acetylation in tumor epithelial-mesenchymal transition (EMT) and migration have not been clearly illuminated. In our research, the immunohistochemistry staining results of skin tissue microarrays showed that HDAC3 staining was increased in CSCC compared with the normal dermal tissue. Then, we found that Rg3 treatment (25 and 50 μg/ml) inhibited CSCC cell (A431 and SCC12 cells) EMT through increasing E-cadherin and decreasing N-cadherin, vimentin, and Snail expression. Wound-healing and transwell assays showed that Rg3 could inhibit migration. Meanwhile, Rg3 significantly downregulated the expression of HDAC3 in CSCC cells as detected by real-time quantitative PCR, western blot, and immunofluorescence. Importantly, c-Jun acetylation was increased by the downregulation of HDAC3 with HDAC3 shRNA, and the downregulation was associated with CSCC cell EMT inhibition. Collectively, our results showed that downregulation of HDAC3 by Rg3 or shHDAC3 treatment resulted in c-Jun acetylation, which in turn inhibited CSCC cell EMT. These results indicate that HDAC3 could potentially serve as a therapeutic target therapeutic target for CSCC. Rg3 is an attractive and efficient agent that has oncotherapeutic effects and requires further investigation.
近年来，人类皮肤鳞状细胞癌（CSCC）的转移率有所增加。尽管目前治疗方法有所进步，但仍缺乏有效的治疗方法。人参皂苷 20(R)-Rg3 是从人参中提取的一种有效的抗肿瘤单体，但 Rg3 在 CSCC 中的作用尚不清楚。据报道，异常升高的组蛋白去乙酰化酶 3（HDAC3）参与了多种恶性肿瘤的肿瘤恶性程度。然而，HDAC3 对肿瘤上皮-间充质转化（EMT）和迁移过程中 c-Jun 乙酰化的调节作用尚未得到明确阐明。在我们的研究中，皮肤组织微阵列的免疫组织化学染色结果表明，与正常真皮组织相比，CSCC 中 HDAC3 染色增加。然后，我们发现 Rg3 处理（25 和 50μg/ml）通过增加 E-钙黏蛋白和减少 N-钙黏蛋白、波形蛋白和 Snail 表达来抑制 CSCC 细胞（A431 和 SCC12 细胞）EMT。划痕愈合和 Transwell 分析表明，Rg3 可以抑制迁移。同时，Rg3 通过实时定量 PCR、western blot 和免疫荧光检测，明显下调 CSCC 细胞中 HDAC3 的表达。重要的是，下调 HDAC3 会增加 c-Jun 乙酰化，这与 CSCC 细胞 EMT 抑制有关。综上所述，我们的结果表明，Rg3 下调 HDAC3 或 shHDAC3 治疗导致 c-Jun 乙酰化，进而抑制 CSCC 细胞 EMT。这些结果表明，HDAC3 可能成为 CSCC 的治疗靶点。Rg3 是一种有吸引力和有效的具有抗肿瘤作用的药物，需要进一步研究。
