Glutamate cysteine ligase (GCL) plays an important role in the intracellular detoxification of cisplatin (CDDP). GCL is composed of a modifier or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). Previously, we showed that the GCL subunits enhanced CDDP-resistance in non-small cell lung cancer (NSCLC) xenografts. In small cell lung cancer (SCLC), it is unclear whether the GCL subunits are essential to CDDP-resistance. We examined the gene expression of GCLM and GCLC in four human SCLC xenografts with the real-time polymerase chain reaction (PCR). An in vivo drug sensitivity test with CDDP was performed on the SCLC xenografts. CDDP-resistance was examined as the growth ratio of the relative volume of the treated xenografts to the controls (T/C%). The expression level of GCLM gene in SCLC was significantly lower than that in NSCLC (p=0.0026, Welch's t-test). One of four SCLC xenografts showed 62% of T/C and this was evaluated as CDDP-resistance, while the other three xenografts were sensitive to CDDP in vivo (Mann-Whitney U-test, p<0.01, one-sided). The expression level of the GCLM gene was significantly correlated to T/C% (Fisher's test, p=0.0289, correlations = 0.975), while the GCLC gene expression level was not associated with T/C%. These results suggest that the overexpression of GCLM is correlated with CDDP-resistance in SCLC xenografts in vivo.

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