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

Abstract

To determine the content of low-spin form of cytochrome P450in primary tumors and liver metastases of the patients with metastatic colorectal cancer (mCRC) and and assess its prognostic significance. The levels of the oxidized and low-spin forms of cytochrome P450in the tissues of patients with mCRC were studied by electron paramagnetic resonance. To detect CYP1A2and CYP1B1isoforms, Western blot analysis was used. The activity of metalloprotreinases was studied by gelatine zymography. 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 P450in primary tumors and liver metastases detected by electron paramagnetic resonance is attributed largely to CYP1B1isoform. The content of low-spin form of cytochrome P450inversely 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 P450in tumor tissues was higher than that of patients with low levels of the enzyme (105months vs 61months). In the primary tumors and liver metastases of patients with mCRC, the content of the low-spin form of cytochrome P450decreased, which correlated inversely with patient's survival.