Ginsenoside 3β-O-Glc-DM (C3DM) enhances the antitumor activity of Taxol on Lewis lung cancer by targeting the interleukin-6/Jak2/STAT3 and interleukin-6/AKT signaling pathways

[摘要] Objective: Nonsmall-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Taxol is an effective chemotherapeutic drug widely used for the treatment of NSCLC. However, the clinical use of Taxol is limited due to the occurrence of adverse side effects under high therapeutic doses. Therefore, it is desirable to explore combination therapy to reduce the dose of chemotherapeutic drugs and achieve excellent outcomes. A biosynthetic ginsenoside, 3-O-β-D-glucopyranosyl-dammar-24-ene-3β, 20S-diol (3β-O-Glc-DM, C3DM) is obtained from microbial fermentation by metabolic engineering. Based on previous study findings, we aimed to explore the mechanism of combination therapy with C3DM and Taxol and its increasing antitumor effect on Lewis lung cancer (LLC) in this study. Materials and Methods: A thiazolyl blue tetrazolium bromide (MTT) assay was performed to evaluate cell viability; the apoptotic effect was studied using cell apoptosis assay. The Lewis tumor xenograft experiment was performed to determine the effects of C3DM combined with Taxol on tumor growth in vivo , and western blotting was performed to analyze protein expressions. Results: C3DM effectively inhibited the proliferation of NSCLC cells. Moreover, C3DM increased the antiproliferative activity of Taxol and significantly enhanced cell apoptosis induced by Taxol in Lewis lung cancer cells. C3DM alone also suppressed Lewis tumor growth and enhanced the antitumor activity of Taxol in vivo . Western blot analysis revealed that the effects of the antiproliferation and apoptosis induction of C3DM treatment alone or in combination with Taxol on Lewis lung cancer were mediated by inhibiting the interleukin-6 (IL-6)/Jak2/STAT3 and IL-6/AKT signaling pathways. Conclusions: The results showed that C3DM has the potential to be used in combination therapy with Taxol against NSCLC.

[学科分类] 内科医学

[关键词] Combination therapy;enhancing antitumor activity;ginsenoside C3DM;nonsmall-cell lung cancer;paclitaxel