The examined cancer cell lines constitutively expressed different variety of HO-1 on mRNA level. Strong expression of HO-1 was observed in HepG2, MCF-7 and A549 cells. A moderate expression of HO-1 was observed in K562 cells, and LS174T cells showed no expression of HO-1. Conclusion: Heme oxygenase-1 could be considered as a new marker in the diagnosis of some cancers, especially hepatomacarcinoma.
Our results also suggest that up-regulation of HO-1 may contribute to tumorogenicity of Inhibitors,research,lifescience,medical some cancers. Therefore, the combination of gene-silencing effect of HO-1 and chemotherapy might be considered as a new modality for the treatment of cancers in which the expression HO-1 is up-regulated. Key Words: Heme oxygenase-1,
gene expression, HepG2, A549, MCF7, K562, cancer cells Introduction Inhibitors,research,lifescience,medical A complex variation in gene expression patterns was found occur in the development and progression of cancer, and the experimental reversal of tumorigenicity.1 Thus, it seems that there is a relation between malignancies and alterations in the expression pattern of some genes. One of the genes, which have been discovered to be involved in the ‘rescue response’ Inhibitors,research,lifescience,medical of the tumor, is heme oxygenase-1 (HO-1).2 Heme oxygenase-1 acts as a cytoprotective agent against oxidative injury and cellular stress both in vitro and in vivo.3 This stress protein, which catalyzes the degradation of heme to biliverdin, carbon monoxide
(CO) and free iron, is the inducible isoform of the three heme oxygenases (HO-1, HO-2 and HO-3). Heme oxygenase-1 and its derivatives also possess anti-inflammatory Inhibitors,research,lifescience,medical properties.2,4 Expression of HO-1 is low under normal physiologic conditions, and a variety of stimuli and activated signalling molecules such as HO-1 substrate heme, reactive oxygen species (ROS), nitric oxide species, prostaglandins, cytokines, growth factors such as insulin, and lipopolysaccharide can up-regulate its expression.5 Important roles for the HO-1 and its products Inhibitors,research,lifescience,medical in tumor progression and formation of metastases as well as resistance to anticancer therapy have been hypothesized.2,6 nearly Thus, the high levels of HO-1 in tumor cells may, at least partly, be responsible for their resistance to anticancer treatment.2 Moreover, HO-1 accelerates vascularization of tumors and increases the metastatic potential of cancer cells, because of its proangiogenic properties. Therefore, the expression of HO-1 is usually increased in tumors, compared with surrounding healthy tissues,7 This was shown in lymphosarcoma, adenocarcinoma, hepatoma, glioblastoma, melanoma, prostate cancers, Kaposi sarcoma, squamous carcinoma, pancreatic cancer, and brain tumors.8-13 Generally, it seems that tumor growth and metastasis is accelerated by HO-1, though it may vary SRT1720 in vitro according to the type of cancer.