In the present study, we found that Ginsenoside Rg3 attenuated the stemness of non-small cell lung cancer (NSCLC) cells, evident by decreasing spheroid formation ability, ALDH1 activity and stemness marker expression. Furthermore, osimertinibresistant NSCLC cells displayed a stronger stemness than the parental cells.Ginsenoside Rg3 reduced the stemness and osimertinib resistance of osimertinibresistant cells. RNA-sequencing revealed that Hippo signaling was shown on the top of the most upregulated pathways regulated by Ginsenoside Rg3 in NSCLC cells, and YAP/TAZ expression was suppressed by Ginsenoside Rg3. Notably, the inhibitor of Hippo signaling attenuated the effects of Ginsenoside Rg3 on the stemness of NSCLC cells. Therefore, Ginsenoside Rg3 attenuates the osimertinib resistance of NSCLC cells via suppressing the stemness, which is dependent on Hippo pathway. K E Y W O R D SGinsenoside Rg3, osimertinib, non-small cell lung cancer, Hippo

Non-small cell lung cancer (NSCLC) is closely associated with inflammation and chronic infection. Antibiotics are frequently prescribed for NSCLC patients in combination with epidermal growth factor receptor (EGFR)-targeted treatment in the presence of infection. The association between antibiotic use and the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has not previously been thoroughly investigated. Therefore, the present study investigated whether antibiotics could affect the efficacy and toxicity of EGFR-TKI treatment, with the aim of restricting the use of antibiotics in combination with targeted therapy in patients with advanced NSCLC in the near future. All patients received treatment with EGFR-TKIs until disease progression, unacceptable toxicity or other factors, including death, pregnancy or unwillingness to further receive targeted therapy, were observed. Patients were retrospectively divided into two groups: Group A, which was treated with EGFR-TKIs and antibiotics; and Group B, which was treated with EGFR-TKIs alone. Patients having used antibiotics 6 months prior to EGFR-TKI therapy were also included in the study. Antibiotic use negatively affected the median progression-free survival (PFS) following EGFR-TKI treatment in NSCLC compared with that in patients not treated with antibiotics; median PFS in Group A was 6.6 months, whereas median PFS in Group B was 10.1 months. Antibiotics also increased the toxicity of targeted therapy for advanced NSCLC. There were significant statistical differences between the two groups in the occurrence of the adverse events of diarrhea and dyspnea. In conclusion, antibiotics decreased the efficacy of first-line targeted therapy in advanced NSCLC and increased incidences of diarrhea and dyspnea. Large randomized studies are needed to identify the impact of antibiotic use on EGFR-TKI treatment for NSCLC.

Objective To analyze the prognostic significance of the pretreatment platelet/lymphocyte ratio (PLR) for targeted therapy in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Methods We conducted a retrospective study of 96 patients with EGFR-mutated advanced NSCLC who were treated at Dongguan People’s Hospital, Southern Medical University from May 2014 to December 2017. All patients received EGFR-targeted therapy until disease progression, unacceptable toxicity, or other factors. Approximately 3 days before the initial treatment, data including a detailed clinical history, physical examination, radiographic results, pathological diagnosis, and laboratory parameters including complete blood cell counts and albumin levels were evaluated. Results Patients in the PLR ≥ 190 group had shorter progression-free survival (PFS) than those in the PLR < 190 group. Furthermore, the 1-year PFS rate was worse in the PLR ≥ 190 group than in the PLR< 190 group. Multivariate analysis indicated the possible role of PLR as a prognostic factor for patients with advanced NSCLC who received EGFR-targeted therapy. Conclusions Pretreatment PLR may be an independent prognostic factor for patients with NSCLC receiving EGFR tyrosine kinase inhibitor treatment. Further studies are needed to identify the impact of PLR on EGFR-mutated NSCLC.