Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis.

BACKGROUND: Intraperitoneal (i.p.) chemotherapy with paclitaxel is a potential therapeutic modality for patients with peritoneal metastasis of gastric cancer. To overcome paclitaxel resistance, which is a major clinical problem with this modality, prediction of i.p. paclitaxel resistance is critically important.

MATERIALS AND METHODS: We developed three new i.p. paclitaxel-resistant cell lines from parental gastric cancer cell lines by an in vivo selection method using i.p. paclitaxel chemotherapy. With these cell lines, we performed gene expression profiling analysis to select up-regulated genes in i.p. paclitaxel-resistant cells and validated the genes with clinical samples.

RESULTS: We successfully isolated nine up-regulated genes in i.p. paclitaxel-resistant cell lines compared with parental cells by microarray analysis, followed by confirmation with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Among these, we identified four genes, namely kinesin family member-23 (KIF23), ERBB2 interacting protein (ERBB2IP), ATPase family, AAA domain containing-2 (ATAD2) and PHD finger protein (PHF19) as candidate genes for paclitaxel resistance after validation with clinical samples derived from responders and non-responders to paclitaxel treatment.

CONCLUSION: These i.p. paclitaxel-resistant cell lines are ideal models for understanding the mechanism of resistance to i.p. paclitaxel and development of a new therapeutic modality. Four up-regulated genes may be potential new predictive markers for resistance to i.p. paclitaxel in patients with peritoneal metastasis of gastric cancer.