Cytochrome P450 content in primary tumors and liver metastases of patients with metastatic colorectal cancer

Abstract

Summary. Aim: To determine the content of low-spin form of cytochrome P450 in primary tumors and liver metastases of the patients with metastatic colorectal cancer (mCRC) and and assess its prognostic significance. Materials and Methods: The levels of the oxidized and low-spin forms of cytochrome P450 in the tissues of patients with mCRC were studied by electron paramagnetic resonance. To detect CYP 1A2 and CYP 1B1 isoforms, Western blot analysis was used. The activity of metalloprotreinases was studied by gelatine zymography. Results: In the liver metastases and tissues adjacent to metastasis, the levels of low-spin forms of cytochrome P450 are lower than in the samples of conventionally normal liver tissue. Western blot analysis revealed that low-spin form of cytochrome P450 in primary tumors and liver metastases detected by electron paramagnetic resonance is attributed largely to CYP 1B1 isoform. The content of low-spin form of cytochrome P450 inversely correlated with the the activity of gelatinases (matrix metalloproteinase-2 and -9). The survival of patients with high levels of the low-spin form of cytochrome P450 in tumor tissues was higher than that of patients with low levels of the enzyme (105 months vs 61 months). Conclusion: In the primary tumors and liver metastases of patients with mCRC, the content of the low-spin form of cytochrome P450 decreased, which correlated inversely with patient’s survival.