Genomic analysis of drug resistant small cell lung cancer cell lines by combining mRNA and miRNA expression profiling

Etoposide (VP16) combined with cisplatin (DDP), as the first-line chemotherapy for small cell lung cancer (SCLC), regularly confers drug resistance. The present study applied complementary (c)DNA and micro (mi)RNA microarray to identify gene and miRNA expression profiles associated with multidrug resistance (MDR) in SCLC. The VP16/DDP (VP16 combined with DDP) resistant SCLC H446/EP cell line was derived from the parental H446 cell line by continuous exposure to increasing concentrations of etoposide and cisplatin. The mRNA and miRNA expression profiles between the resistant and parental SCLC cells were analyzed by Phalanx OneArray™ mRNA and miRNA microarray, and the results were confirmed by quantitative polymerase chain reaction. The expression levels of 75 genes were downregulated whilst 40 genes were upregulated in the H446/EP cell line compared with the H446 cell line. The expression levels of 16 miRNAs were upregulated whilst 15 were downregulated in the H446/EP cell line compared with the H446 cell line. Expression profile studies indicate that the particular mRNA and miRNA alteration demonstrated in MDR of SCLC may provide potential biomolecular targets for MDR reversion.