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人参皂苷Rg3增强吉非替尼在肺癌细胞系中的抗肿瘤活性。

Ginsenoside Rg3 promotes the antitumor activity of gefitinib in lung cancer cell lines.

作者信息

Dai Yuemei, Wang Wenran, Sun Qingchao, Tuohayi Jiazina

机构信息

Department of Respiratory Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.

Department of Cancer, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.

出版信息

Exp Ther Med. 2019 Jan;17(1):953-959. doi: 10.3892/etm.2018.7001. Epub 2018 Nov 21.

Abstract

Lung cancer is one of the most common types of cancer with one of the highest incidence and mortality rates. Gefitinib is widely used for the treatment of non-small cell lung cancer (NSCLC). However, issues regarding drug resistance, toxicity and limited applicability have been associated with gefitinib. The aim of the present study was to investigate whether ginsenoside Rg3 enhances the anticancer activity of gefitinib in NSCLC cells. MTT assay demonstrated that ginsenoside Rg3 increased the cytotoxic effect of gefitinib in NSCLC cell lines in a dose- and time-dependent manner. In addition, flow cytometric analysis revealed that the combined treatment with gefitinib and ginsenoside Rg3 significantly increased apoptosis in NSCLC cell lines. Transwell migration assays demonstrated that the combined treatment with gefitinib and ginsenoside Rg3 significantly decreased NSCLC cell migration compared with gefitinib or ginsenoside Rg3 treatment alone. Furthermore, western blot analysis revealed that in NSCLC cell lines, the combined treatment with gefitinib and ginsenoside Rg3 increased protein expression levels of pro-apoptotic proteins Bax and cleaved-caspase-3, whilst the expression level of anti-apoptotic protein Bcl-2 decreased. In addition, western blot analysis revealed that, in NSCLC cell lines, the combined treatment with gefitinib and ginsenoside Rg3 decreased the protein expression levels of pro-migration factors SNAIL and SLUG, whilst the expression level of anti-migration protein E-cadherin increased. In conclusion, ginsenoside Rg3 may be able to enhance the anticancer activity of gefitinib, making NSCLC cells more sensitive to gefitinib.

摘要

肺癌是最常见的癌症类型之一,其发病率和死亡率都很高。吉非替尼被广泛用于治疗非小细胞肺癌(NSCLC)。然而,与吉非替尼相关的耐药性、毒性和适用性有限等问题一直存在。本研究的目的是探讨人参皂苷Rg3是否能增强吉非替尼对NSCLC细胞的抗癌活性。MTT试验表明,人参皂苷Rg3以剂量和时间依赖性方式增加了吉非替尼对NSCLC细胞系的细胞毒性作用。此外,流式细胞术分析显示,吉非替尼与人参皂苷Rg3联合治疗显著增加了NSCLC细胞系的凋亡。Transwell迁移试验表明,与单独使用吉非替尼或人参皂苷Rg3治疗相比,吉非替尼与人参皂苷Rg3联合治疗显著降低了NSCLC细胞的迁移。此外,蛋白质印迹分析显示,在NSCLC细胞系中,吉非替尼与人参皂苷Rg3联合治疗增加了促凋亡蛋白Bax和裂解的半胱天冬酶-3的蛋白表达水平,而抗凋亡蛋白Bcl-2的表达水平降低。此外,蛋白质印迹分析显示,在NSCLC细胞系中,吉非替尼与人参皂苷Rg3联合治疗降低了促迁移因子SNAIL和SLUG的蛋白表达水平,而抗迁移蛋白E-钙黏蛋白的表达水平增加。总之,人参皂苷Rg3可能能够增强吉非替尼的抗癌活性,使NSCLC细胞对吉非替尼更敏感。

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