Expression Profiling Of ATP-binding Cassette Transporters In A Paclitaxel-resistance Nasopharyngeal Carcinoma Cell Line

Objective: To screen some genes associated with drug-resistance in paclitaxel-resistance nasopharyngeal carcinoma cells utilizing Affymetrix Human Genome U133 Plus 2.0 Array and focus on analysising the effect of ATP-binding cassette (ABC) transporters in the process of paclitaxel-resistance.Method: 1. The colony formation assay was carried out to detect the resistance index of paclitaxel-resistance nasopharyngeal carcinoma cells(CNE1/Taxol). 2. To extract RNA from the paclitaxel treated and untreated nasopharyngeal carcinoma cells and resistance cells, then carried out the Affymetrix GeneChip Expression Assay. 3. To analyze the difference of gene expression between CNE-1/Taxol and CNE-1 by GCOS and dChip software.Result: 1. The colony formation assay was carried out three times and the half inhibiting concentration (7.98ng/ml) and resistance index (7.00±0.62) of paclitaxel-resistance nasopharyngeal carcinoma cells were determined. 2. Microarray analysis showed that eight genes were highly expressed in CNE-1/Taxol comparing with CNE-1, and their expression continued to be increased in CNE1/Taxol treated by IC₅₀ paclitaxol. These genes were MB(myoglobin), MAOA (monoamine oxidase A), FOLR1 (folate receptor 1), DNER(d-notch-like EGF repeat-containing transmembrane), OR2A7 (olfactory receptor, family 2, subfamily A, member 7), CFH(complement factor H), DERP12(dermal papilla derived protein 12)and KIAA0500 (KIAA0500 protein). 3. Eight ATP-binding cassette transporters that highly expressed in paclitaxel-resistance nasopharyngeal carcinoma cells were detected. These genes were ABCA7(ATP-binding cassette, subfamily A, member 7), ABCB10(ATP-binding cassette, subfamily B, member 10), ABCC1(multidrug resistance-related protein 1, MRP1), ABCC4(multidrug resistance-related protein 4, MRP4), ABCC5(multidrug resistance-related protein 5, MRP5), ABCC6(multidrug resistance-related protein 6, MRP6), ABCD3(ATP-binding cassette, subfamily D, member 3) and ABCG2(breast cancer resistance protein, BCRP). However, the expression of these genes showed to be not increased in CNE-1/Taxol cells after treated by IC₅₀ paclitaxel. Conclusion: 1. After cDNA microarray experiment, eight genes were detected to be highly expressed in CNE1/Taxol, and their expression continued to be increased in CNE-1/Taxol treated by IC₅₀ paclitaxol. It indicated that these eight genes were related to paclitaxel-resistance in nasopharyngeal carcinoma cells. 2. Eight members of ATP-binding cassette transporter superfamily showed an increase of mRNA expression, and which indicated their relationship to paclitaxel drug-resistance in nasopharyngeal carcinoma cells. However, they may not critical genes.