Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, P.R. China.
Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, P.R. China.
Anticancer Agents Med Chem. 2023;23(13):1596-1604. doi: 10.2174/1871520623666230413130417.
Hook F provided the source of the first diterpenoid triepoxide lactone, Triptolide, identified as the primary constituent causing the anticancer activity. So far, it has not been reported whether triptolide has a therapeutic effect on cutaneous squamous cell carcinoma (cSCC).
This study investigates the triptolide's therapeutic impact on cSCC both in vitro and in vivo and investigates the triptolide's potential involvement in signaling pathways.
The CCK-8 assays, wound healing assays, and colony formation assays were used to assess the effects of triptolide on the proliferation and migration of cSCC cells. The alteration in gene expression following triptolide treatment was shown by RNA sequencing. Flow cytometry was then applied to evaluate cell apoptosis. Western blot was used to find the associated proteins' expressions. The effectiveness of triptolide was then evaluated in vivo using a xenograft model, and histological staining was employed to determine the visceral toxicity.
Triptolide greatly reduces the migratory and proliferative capacity of cSCC cells. Triptolide dramatically decreased cell viability and migration in the A431 and SCL-1 cells compared to the control group, according to the CCK8 assay, wound healing assay, and colony formation assay. Flow cytometry demonstrated that treatment with 10- 40 nM triptolide increased apoptosis in a concentration-dependent manner, with a statistically significant difference. Furthermore, mice given triptolide had smaller tumor sizes than those in the control group. Triptolide treatment drastically altered the expression of autophagic and apoptotic proteins. The considerable reduction in the proteins Akt and mTOR levels further illustrated the critical function of triptolide in cSCC.
Triptolide caused cSCC cells to engage in autophagy and apoptosis by inhibiting the Akt/mTOR signaling pathways. Triptolide may be a possible antitumor agent for the treatment of cSCC.
钩藤提供了第一个二萜三环氧内酯，雷公藤内酯，被鉴定为具有抗癌活性的主要成分的来源。到目前为止，还没有报道雷公藤内酯是否对皮肤鳞状细胞癌（cSCC）有治疗作用。
本研究探讨雷公藤内酯对 cSCC 的体内外治疗作用，并探讨雷公藤内酯在信号通路中的潜在作用。
用 CCK-8 法、划痕愈合实验和集落形成实验评估雷公藤内酯对 cSCC 细胞增殖和迁移的影响。用 RNA 测序显示雷公藤内酯处理后基因表达的变化。然后用流式细胞术评估细胞凋亡。用 Western blot 检测相关蛋白的表达。用异种移植模型评价雷公藤内酯的疗效，并进行组织学染色以确定内脏毒性。
雷公藤内酯显著降低 cSCC 细胞的迁移和增殖能力。与对照组相比，CCK8 法、划痕愈合实验和集落形成实验显示，雷公藤内酯显著降低 A431 和 SCL-1 细胞的细胞活力和迁移。流式细胞术表明，用 10-40 nM 雷公藤内酯处理可呈浓度依赖性增加细胞凋亡，差异有统计学意义。此外，与对照组相比，给予雷公藤内酯的小鼠肿瘤体积更小。雷公藤内酯处理显著改变自噬和凋亡蛋白的表达。蛋白 Akt 和 mTOR 水平的显著降低进一步说明了雷公藤内酯在 cSCC 中的关键作用。
雷公藤内酯通过抑制 Akt/mTOR 信号通路使 cSCC 细胞发生自噬和凋亡。雷公藤内酯可能是治疗 cSCC 的一种潜在抗肿瘤药物。
