Correlation of peroxisome pathway reactive oxygen species oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer

Abstract

Objective To explore the screening of peroxisome pathway reactive oxygen species (ROS) oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer. Methods Based on microarray mRNA expressions of 55 tumor cell lines in the National Cancer Institute common database, peroxisome pathway-related key genes which were significant correlation with half-inhibitory concentration (IC50) values of artesunate antitumor activity against human pancreatic cancer were selected by Kendall test. The candidate genes associated with artesunate sensitivity were identified and their mRNA expressions in pancreatic cancer cells were tested using fluorescent quantitative PCR. The contents of peroxidase in pancreatic cancer cells were detected through the DAB staining. Results Thirteen key genes mRNA expressions in peroxidase pathways were significantly correlated with IC50 values for artesunate antitumor activity. Compared with normal liver cells HL-7702 (1.00), CRAT (2.89±0.06), PEX11B (1.90±0.07) and PEX16 (1.35±0.07) mRNA expression levels were significantly increased in pancreatic cancer Panc-1 cells which sensitive to artesunate (t=33.00, P<0.01; t=17.85, P<0.01; t=4.54, P<0.05). While CAT (1.43±0.03), SOD1 (2.07±0.04) and SOD2 (1.15±0.01) mRNA expression levels were also significantly increased in Panc-1 cells which sensitive to artesunate (t=11.71, P<0.01; t=35.85, P<0.01; t=13.22, P<0.01). However, PEX12 (0.51±0.02), CAT (0.47±0.02), PRDX1 (0.43±0.01), and SOD1 (0.44±0.01) mRNA expression levels in pancreatic cancer BXPC-3 cells which resistant to artesunate were significantly lower than that of HL-7702 cells (t=37.53, P<0.01; t=16.52, P<0.01; t=84.20, P<0.01; t=48.24, P<0.01). DAB staining showed that the positive expression rate of peroxisomal content was apparently higher in Panc-1 cells (61.5%) than that of HL-7702 cells (43.8%), with a significant difference (χ2=16.11, P<0.01). Conclusion Peroxisome and its related ROS antioxidant enzymes CAT, PRDX1, SOD gene expression may be the important factors that affect artesunate antitumor activity against human pancreatic cancer. Key words: Pancreatic neoplasms; Peroxisomes; Reactive oxygen species; Antineoplastic agents; Artesunate