Patient-derived organoids of non-small cells lung cancer and their application for drug screening

Yun-Feng Li, Yuan Gao, Bo-Wen Liang, Xiao-Qing Cao, Zhi-Jian Sun, Jian-Hua Yu,  Zhi-Dong Liu,  Yi Han

Abstract:

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, 7.50–10.45 μM and 4.27–6.50 μM in PDOs, 3.07–4.44 μM and 4.69–544.99 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.