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

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.

The Efficacy of Ginsenoside Rg3 Combined with First-line Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“… Liu et al (2019) Reported that ginsenoside Rg3 could upregulate VRK1 expression and P53BP1 foci formation in response to DNA damage, thereby inhibiting the tumorigenesis and viability of cancer cells. Futhermore, ginsenoside Rg3 could enhance the anticancer activity of Gefitinib through increasing apoptosis and decreasing migration in NSCLC cell lines ( Dai et al, 2019 ). Therefore, ginsenoside Rg3 can effectively improve the efficacy and reverse drug resistance, suggesting that it can be used as an adjuvant in clinical treatment to benefit NSCLC patients.…”

Effects of Ginsenoside Biopolymer Nanoparticles on the Malignant Behavior of Non-Small-Cell Lung Cancer

“…However, with that comes the toxic side e ects and higher recurrence rate, and it is also demanding in terms of the patient's physical quality. In recent years, the advantages of traditional Chinese medicine in cancer treatment have gradually gained attention, which can reduce the side e ects of radiotherapy and chemotherapy on patients, prolong the quality lifespan of patients, and alleviate the drug resistance in the cancer treatments [5][6][7]. Ginsenoside Rg3 is the active ingredient extracted from ginseng.…”

“…Wu et al [8] reported that ginsenoside Rg3 can inhibit the proliferation of thyroid cancer in vitro and in vivo and signi cantly inhibit the metastasis of thyroid cancer. Dai et al [5] showed that ginsenoside Rg3 could enhance the anticancer activity of ge tinib and enhance the sensitivity of non-small-cell lung cancer to ge tinib. At present, the "Senyi Capsule" containing ginsenoside Rg3 has been approved for marketing in China and has been used for clinical treatment of cancer, which has achieved a certain curative e ect.…”

Anticancer Activities of Ginsenosides, the Main Active Components of Ginseng

“…Ginsenosides have been known to improve the efficiency of currently used treatments against lung cancer. Rg3 improved sensitivity and suppressed resistance to several drugs, such as icotinib, gefitinib, cisplatin, gemcitabine, and osimertinib [ 123 – 128 ]. Several studies observed that Rk1 and Rg3 restricted programmed death ligand 1 (PD-L1) expression, Rg3 improved the efficacy of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), and Rd downregulated the NRF2 pathway to decrease acquired chemoresistance [ 128 – 131 ].…”