Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 μM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 μM) and cell lines (1.45-3.73 μM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 μM), whereas cell lines showed a resistance (95% CI, 46.57-2275 μM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0. 05, μM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

Recent studies demonstrated that bone mesenchymal stem cells (BMSCs) can be recruited to the tumor microenvironment, and exosomes secreted by BMSCs have new function in the intercellular communication of human cancer. To explore the effects of human BMSCs-derived exosomal miR-126 on the proliferation, migration and invasion of colon cancer. BMSCs were transfected with mimic and inhibitor of miR-126, respectively. Then after BMSCs treated with mimic or inhibitor, we isolated exosomes from BMSCs. The viability, migration and invasion ability of Colon cells were detected via methyl thiazolyl tetrazolium (MTT) assay and Transwell assay, respectively. The targeting relation between miR-126 and plexin-B2 (PLXNB2) was verified by using bioinformatics analysis and dual luciferase reporter assay. The expressions of PLXNB2 and related proteins in Colon cells were determined by Western blot. miR-126 expressed higher in exosomes from BMSCs, compared with control group. Moreover, overexpression of miR-126 inhibited cell viability, migration and invasion. In addition, Exosomal miR-126 lead to targeted inhibition of PLXNB2 in Colon cells. What’s more, according to the analysis of exosome content, miR-126 could mediate the inhibitory effect of exosomes on HCT116 and SW620 cells via negative regulating of PLXNB2. The results of our study showed that BMSCs-derived exosomal miR-126 could inhibit cell viability, cell migration and cell invasion.