FIGURE 2.

Establishment of etoposide and SN‐38 resistant small cell lung cancer (SCLC) cells. (a–d) tetrazolium (MTS) assay with topoisomerase inhibitors in established etoposide and SN‐38 resistant SCLC cells. We established two etoposide and SN‐38 resistant SBC‐3 and SBC‐5 sublines (SBC‐3/VR A, B, SBC‐5/VR A, B, SBC‐3/SR A, B, SBC‐5/SR A, B) by continuous exposure to increasing concentrations of etoposide and SN‐38. (e) RNA sequencing data (etoposide and SN‐38 resistant SCLC cells compared to sensitive parental cells). The cut‐off was over four times for resistant compared to parental sensitive lines in both SBC‐3 and SBC‐5 cell lines. Thirty‐seven and 60 genes in response to etoposide and SN‐38, respectively, were induced. ATP‐binding cassette sub‐family B member 1 (ABCB1) was overexpressed in etoposide‐resistant cells and ATP‐binding cassette sub‐family G member 2 (ABCG2) was overexpressed in SN‐38‐resistant cells compared with parental cells for both SBC‐3 and SBC‐5 cell lines (Table S1). (f) Protein expression of etoposide and SN‐38 resistant cells. Whenever the subclones resistant to etoposide showed high ABCB1 expression, the two subclones resistant to SN‐38 showed high ABCG2 expression. GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; TOP, topoisomerase. *p < 0.05 compared to parental cells