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

The current study aimed at exploring the diversity of bacterial lactase genes in the intestinal mucosa of mice with dysbacterial diarrhea induced by antibiotics and to provide experimental basis for antibiotics-induced diarrhea. Mice model of dysbacterial diarrhea was established by gastric perfusion with mixture of cephradine capsules and gentamicin sulfate (23.33 mL kg d), twice a day and continuously for 5 days. Intestinal mucosa from jejunum to ileum was collected, and bacterial metagenomic DNA was extracted for Miseq metagenome sequencing to carry out diversity analysis. The results showed that specific operational taxonomic units (OTUs) were 45 in the control group and 159 in the model group. The Chao1, ACE, Shannon and Simpson indices in model group were significantly higher (< 0.01 or < 0.05) than control group. Principal component analysis (PCA) and box chart of the control group were relatively intensive, while in the model group, they were widely dispersed. Furthermore, the inter-group box area was higher than that in the intra-group. Compared with the model group, the abundance of bacterial lactase genes in Proteobacteria from the intestinal mucosa of the control group was higher, but lower in Actinobacteria and unclassified bacteria. At the genus level, the relative abundance of bacterial species and taxon units in model group was obviously increased (< 0.05). Our results indicate that antibiotics increased the diversity and abundance of bacterial lactase genes in the intestinal mucosa, as the abundance of ,, ,, and. In addition, antibiotics become an additional source for lactase genes of ,, ,, and.

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.

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