Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis.
Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis.
复制标题
DOI：
--
复制
发表时间：
2013-10
影响因子：
2
通讯作者：
Hiroki Murakami;S. Ito;Harunari Tanaka;E. Kondo;Y. Kodera;H. Nakanishi
中科院分区：
文献类型：
--
作者：
Hiroki Murakami;S. Ito;Harunari Tanaka;E. Kondo;Y. Kodera;H. Nakanishi
背景腹膜内（i. p.）紫杉醇化疗是一种潜在的治疗胃癌腹膜转移的方法。为了克服紫杉醇耐药性（这是这种治疗方法的一个主要临床问题），预测腹膜内紫杉醇耐药性至关重要。材料和方法我们通过使用腹膜内紫杉醇化疗的体内选择方法从亲本胃癌细胞系开发了三种新的腹膜内紫杉醇耐药细胞系。利用这些细胞系，我们进行了基因表达谱分析，以选择腹膜内紫杉醇耐药细胞中上调的基因，并利用临床样本验证了这些基因。结果通过基因芯片分析成功分离出9个在紫杉醇耐药细胞中表达上调的基因，并通过定量逆转录-聚合酶链反应（qRT-PCR）进行了验证。其中，我们确定了四个基因，即驱动蛋白家族成员-23（KIF 23），ERBB 2相互作用蛋白（ERBB 2 IP），ATP酶家族，AAA结构域包含-2（ATAD 2）和PHD指蛋白（PHF 19）作为候选基因的紫杉醇耐药后，与临床样本的验证来自反应者和非反应者的紫杉醇治疗。结论腹腔注射紫杉醇耐药细胞系是研究腹腔注射紫杉醇耐药机制和开发新的治疗方法的理想模型。四个上调基因可能是胃癌腹膜转移患者腹腔注射紫杉醇耐药的新的预测指标。
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.