Correlation Of Gene Polymorphisms And MRNA Expression Levels With Chemosensitivity To First Line Anticancer Drugs For Lung Cancer In Human NSCLC Cell Lines

Objective: Significant variability in the efficacy and toxicity of anticancer drugshas been observed in lung cancer patients. Currently, there are no standard tools forpredicting a patient’s tumor response or his risk of adverse events to chemotherapy.We used a panel of17non-small cell lung cancer (NSCLC) cell lines to investigatewhether gene polymorphisms or mRNA expression levels correlated with in vitrochemosensitivity to anticancer drugs.Methods: Polymorphisms of the genes were evaluated by direct sequencing.mRNA expression levels were examined by quantitative real-time reversetranscription PCR. The in vitro chemosensitivity to gemcitabine, cisplatin andpaclitaxel were expressed as IC50using a tetrazolium-based colorimetric assay (MTTassay).Results:1. There is a significant positive correlation between RRM1mRNAexpression level and IC50values for gemcitabine (r=0.6533, p=0.0045). It meansthat we can predict the drug response of gemcitabine if the RRM1mRNA expressionlevel was determined before treatment. The polymorphisms of RRM12455A>G and2464G>A are not associated with chemosensitivity of gemcitabine (p=0.2980and p=0.1394). The polymorphism of RRM12455A>G is associated with RRM1expression level (p=0.0298). However, the polymorphism of RRM12464G>A is notassociated with RRM1expression (p=0.0856).2. There is no significant correlationbetween ERCC1mRNA expression level and IC50values for cisplatin (r=-0.1834, p=0.4812). The polymorphism of ERCC18092C>A is not associated with IC50values (p=0.6070). The polymorphism of ERCC18092C>A is associated with ERCC1expression (p=0.0186).3. There is a significant positive correlation between ABCB1mRNA expression level and IC50values for paclitaxel (r=0.5322, p=0.0279). Itmeans that we can predict the drug response of paclitaxel if the ABCB1mRNAexpression level was determined before treatment. None of the ABCB1genepolymorphisms of2677G>T/A,2734T>C,3396C>T and3435C>T correlate withpaclitaxel chemosensitivity or to mRNA expression level in the17NSCLC cell lines.Conclusions: These in vitro results suggest that the mRNA expression level ofthe genes could be a predictive biomarker for chemosensitivity to anticancer drugs.The chosen panel of cell line is capable of providing clues and indications for theestablishment of clinically useful relationships between a given polymorphism orgene expression level and chemosensitivity to an anticancer agent.