Relationship between drug sensitivity of gastric cancer tissues to L-oxaliplatin and microRNA-150

Abstract

Objective To explore relationship between drug sensitivity of gastric caner tissues to L-oxaliplatin (L-OHP) and microRNA (miRNA, miR)-150 and its significance. Methods Specimens of gastric cancer tissues and cancer-adjacent normal tissues from 80 patients were collected. The expression levels of miR-150 and mRNA of multidrug resistance gene 1 (MDR1), glutathione S transferase-π (GST-π), B cell lymphoma/leukemia-2 (bcl-2) and Survivin were detected by real-time quantitative polymerase chain reaction (Real-time PCR), and those of P-glycoprotein (P-gp), GST-π, bcl-2 and Survivin proteins were detected by immunohistochemistry. Methyl thiazol tetrazolium (MTT) assay was utilized to test sensitivity of gastric cancer tissues and cancer-adjacent normal tissues to L-OHP. Results The expression level of miR-150 in gastric cancer tissues (0.324 1±0.063 6) was significantly lower than in cancer-adjacent normal tissues (0.576 0±0.148 0) (t=-13.987, P=0.000), and those of MDR1, GST-π, bcl-2 and Survivin mRNAs [(1.217 7±0.272 6), (0.695 3±0.256 7), (0.898 5±0.196 2), (0.826 2±0.270 8), respectively] were all higher than in cancer-adjacent normal tissues [(0.302 0±0.092 1), (0.347 7±0.162 8), (0.195 2±0.085 6), (0.348 6±0.172 0), respectively] (t=28.464, P=0.000; t=10.228, P=0.000; t=29.387, P=0.000; t=13.316, P=0.000). Results of MTT assay showed that relative cell activty to L-OHP was (62.11±25.65)%; cell activity in high-expressed miR-150 group [(52.02±28.71)%] was weaker than in low-expressed miR-150 [(73.27±15.73)%] (t=-4.045, P=0.000); cell activity in positively expressed P-gp, bcl-2, Survivin proteins groups was stronger than in negatively expressed groups, while no association was verified between cell activity (treated with L-OHP) and expression of GST-π (t=0.228, P=0.821). Negative correlation was presented between miR-150 and MDR1, or between miR-150 and bcl-2 (r=-0.571, P=0.000; r=-0.561, P=0.000); while no significant correlations were found between miR-150 and GST-π, or between miR-150 and Survivin (r=0.0882, P=0.437; r=0.186, P=0.098). Conclusion miR-150 might be involved in drug resistance of gastric cancer cells to L-OHP by regulating MDR1, bcl-2 genes. Key words: MicroRNA-150; Gastric cancer; Oxaliplatin; Drug resistance