Huang Lu-Lu, Tang Mei, Du Qian-Qian, Liu Chun-Xia, Yan Chen, Yang Jin-Ling, Li Yan
Department of Pharmacology, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
Onco Targets Ther. 2019 Sep 9;12:7375-7385. doi: 10.2147/OTT.S217039. eCollection 2019.
A biosynthetic ginsenoside, 3-O-β-D-glucopyranosyl-12-O-β-D-glucopyranosyl-dammar-24-ene-3β, 12β, 20S-triol (CCPPD), showed antitumor activity against many tumor cells in vitro, especially had better anti-lung cancer activity than Rg3 in vitro and in vivo. However, the effects and molecular mechanisms of CCPPD on non-small cell lung cancer (NSCLC) remain unclear. According to previous studies, we hypothesized ginsenoside CCPPD could inhibit the tumor growth of NSCLC by targeting proliferation, migration and angiogenesis.
A thiazolyl blue tetrazolium bromide assay (MTT) was performed to evaluate cell viability. Additionally, Transwell and tube formation assays were conducted to analyze cell migration and angiogenesis. The Lewis and A549 tumor xenograft experiments were also performed to investigate the effects of CCPPD on tumor growth in vivo, Western blotting and IHC assay were performed to analyze protein expression.
CCPPD could effectively inhibit the proliferation and migration of lung cancer cells, and tube formation of EA.hy926 cell. Ginsenoside CCPPD suppressed Lewis and A549 tumor growth in vivo without obvious side effects on body weight and the hematology index. In addition, the Western blot analysis revealed that the effects of CCPPD on lung cancer were mediated by inhibiting Raf/MEK/ERK, AKT/mTOR and AKT/GSK-3β/β-Catenin signaling pathways. Finally, CCPPD could significantly inhibit the proliferation index and vessel number in Lewis xenograft tumors analyzed by IHC.
The results of the present study suggest that ginsenoside CCPPD may serve as a potential therapeutic candidate compound against NSCLC.
一种生物合成人参皂苷，3 - O - β - D - 吡喃葡萄糖基 - 12 - O - β - D - 吡喃葡萄糖基 - 达玛烷 - 24 - 烯 - 3β，12β，20S - 三醇（CCPPD），在体外对多种肿瘤细胞显示出抗肿瘤活性，尤其是在体外和体内均比Rg3具有更好的抗肺癌活性。然而，CCPPD对非小细胞肺癌（NSCLC）的作用及分子机制仍不清楚。根据以往研究，我们推测人参皂苷CCPPD可能通过靶向增殖、迁移和血管生成来抑制NSCLC的肿瘤生长。
进行噻唑蓝四唑溴盐比色法（MTT）以评估细胞活力。此外，进行Transwell实验和管腔形成实验以分析细胞迁移和血管生成。还进行了Lewis和A549肿瘤异种移植实验以研究CCPPD对体内肿瘤生长的影响，进行蛋白质印迹法和免疫组化分析以分析蛋白质表达。
CCPPD可有效抑制肺癌细胞的增殖和迁移以及EA.hy926细胞的管腔形成。人参皂苷CCPPD在体内抑制Lewis和A549肿瘤生长，且对体重和血液学指标无明显副作用。此外，蛋白质印迹分析显示，CCPPD对肺癌的作用是通过抑制Raf/MEK/ERK、AKT/mTOR和AKT/GSK - 3β/β - 连环蛋白信号通路介导的。最后，免疫组化分析显示CCPPD可显著抑制Lewis异种移植肿瘤中的增殖指数和血管数量。
本研究结果表明人参皂苷CCPPD可能是一种潜在的抗NSCLC治疗候选化合物。
