OncoTargets and Therapy (Sep 2019)
The effects and mechanisms of a biosynthetic ginsenoside 3β,12β-Di-O-Glc-PPD on non-small cell lung cancer
Abstract
Lu-Lu Huang,1,2 Mei Tang,1,2 Qian-Qian Du,1,2 Chun-Xia Liu,1,2 Chen Yan,2 Jin-Ling Yang,3 Yan Li1,2 1Department 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; 2Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China; 3Department of Biosynthesis, State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Key Laboratory of Biosynthesis of Natural Products of National Health and Family Planning Commission, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Yan LiInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, People’s Republic of ChinaTel +86 10 6316 9181Email [email protected]: A biosynthetic ginsenoside, 3-O-β-D-glucopyranosyl-12-O-β-D-glucopyranosyl-dammar-24-ene-3β, 12β, 20S-triol (C3C12PPD), 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 C3C12PPD on non-small cell lung cancer (NSCLC) remain unclear. According to previous studies, we hypothesized ginsenoside C3C12PPD could inhibit the tumor growth of NSCLC by targeting proliferation, migration and angiogenesis.Methods: 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 C3C12PPD on tumor growth in vivo, Western blotting and IHC assay were performed to analyze protein expression.Results: C3C12PPD could effectively inhibit the proliferation and migration of lung cancer cells, and tube formation of EA.hy926 cell. Ginsenoside C3C12PPD 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 C3C12PPD on lung cancer were mediated by inhibiting Raf/MEK/ERK, AKT/mTOR and AKT/GSK-3β/β-Catenin signaling pathways. Finally, C3C12PPD could significantly inhibit the proliferation index and vessel number in Lewis xenograft tumors analyzed by IHC.Conclusion: The results of the present study suggest that ginsenoside C3C12PPD may serve as a potential therapeutic candidate compound against NSCLC.Keywords: C3C12PPD, NSCLC, Raf/MEK/ERK, AKT/mTOR, AKT/GSK-3β/β-Catenin
