Screening The Genes Related With Cisplatin Resistance And Sensitivity In Primary Lung Cancers Using CDNA Microarray Technology

Objective: To investigate the genes correlated with DDP resistance and sensitivity in NSCLC (non-small cell lung cancer) using cDNA microarray technology.Methods: The drug sensitivities of DDP (cisplatin) in NSCLC were examined by MTT agarose method. According to the inhibition rate in vitro, clinical samples were identified to be sensitivity and resistance to drugs, respectively. After extracting RNA from these samples, we analyze gene expression profiles that may be related with DDP resistance by cDNA microarray technology. Results: Out of 93 lung cancer samples,30 showed good linear correlation at 1PPC concentration of DDP. If the inhibition rate of lung-cancer cells is above 50%, this sample is sensitive; if between 30% and 50%, it is moderate sensitive; if below 30%,it is drug resistant. Among 50 samples, 4 are highly sensitive(8%), 15 are moderate sensitive (30%), 31 are drug resistant(62%). This result is in accordance with the previous clinical report that the respondence rate to DDP only is about 21%.According to the result of drug sensitivity experiment,we choose 9 samples ( 3 sensitive, 6 drug-resistant) in our microarray experiment. We find that gene profiles relate with the samples' histologic type and drug sensitivity, using gene cluter analysis of microarray experiment data. Sample 1 and sample 5 are sensitive ones, moreover, they are all squamous. Sample 8 is also sensitive one ,but is not cluster with land 5.Using gene cluster and SAM analysis, We find that up-regulation of some genes (PDCD5, P53AIP1,MOG) is positively related with DDP resistance, and up-regulation of some genes(CDH15,DLX4,M-cadherin,RAD23A,RAD23B) is negatively related with DDP resistance.