zearalenone and Stomach-Neoplasms

The present study aimed to investigate the expression and role of transforming growth factor (TGF) ‑β‑activated protein kinase 1 (TAK1) in human gastric cancer. Immunohistochemistry was performed to investigate the expression of TAK1 in surgical specimens of human gastric cancer tissue and adjacent normal tissue. The association between TAK1 and clinicopathologic factors was analyzed and the association between TAK1 expression and the overall survival rates was evaluated using Kaplan‑Meier curves. In addition, the effect of the TAK1 selective inhibitor 5Z‑7‑oxozeaenol (OZ) on the biological characteristics of MGC803 human gastric cancer cells in vitro were investigated. The role of TAK1 in gastric cancer cell proliferation, apoptosis and invasion were determined by cell proliferation assays, flow cytometry analysis and transwell invasion assays, respectively. The findings of the present study demonstrated that the positive expression rate of TAK1 in gastric cancer and adjacent normal tissues was 70.5 and 25.9%, respectively. Furthermore, TAK1 expression was significantly associated with advanced N stage and pathological stage (P<0.05). Survival analysis of 139 patients with gastric cancer indicated a lower overall survival rate of patients in the TAK1‑positive group compared with the TAK1‑negative group (P<0.05). In addition, treatment with the TAK1 selective inhibitor OZ reduced the proliferation and invasion abilities of MGC803 cells and significantly reduced the expression levels of phosphorylated‑TAK1 (Thr187), nuclear p65, cyclin D1, Bcl‑2 apoptosis regulator and matrix metallopeptidase (MMP)9 (P<0.05). OZ treatment significantly increased the expression levels of cytosolic cytochrome c and cleaved caspase 3 and the apoptosis rate in MGC803 cells (P<0.05). In conclusion, these findings suggest that increased TAK1 expression may be involved in the progression of gastric cancer; therefore, TAK1 may be used as a future therapeutic target for gastric cancer treatment.

Topics: Adult; Aged; Apoptosis; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; MAP Kinase Kinase Kinases; Middle Aged; Neoplasm Invasiveness; NF-kappa B; Phosphorylation; Stomach Neoplasms; Zearalenone

This is the first report to demonstrate the presence of a group of mycotoxins in corn-staple food of Linxian residents, including Nivalenoal (NIV), Deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl-deoxynivalenol (15-ADON), T-2 toxin (these 5 toxins belong to trichothecenes) and zearalenone (ZEN). These 6 toxins were produced by Fusarium species. Using TLC, HPLC, GC, monoclonal antibody affinity column chromatography combined with RIA, respectively, 107 corn samples from Linxian and 2 rice samples from USA were analyzed. It was demonstrated that the average level of NIV was 757 +/- 707(54-2,760)ng/g, DON was 5,376 +/- 4,460 (360-12,670) ng/g with 100% positivity in corn samples consumed as staple food by esophageal cancer patients and their families. Corn samples collected from 5 villages in Linxian at different seasons in 1984-1986 all showed high levels of NIV and DON with 100% positivity which suggested that NIV and DON were consistently and widely existed in Linxian corn samples. Levels of 3-ADON and 15-ADON in Linxian corn were 113 +/- 57 and 495 +/- 538 ng/g. This paper also first demonstrates that the extracts of corn from esophageal cancer patients' families and their NIV and DON fractions purified by HPLC could induce significant chromosome aberrations in V79 cells, indicating that they had carcinogenic potential. Pure toxins of NIV, DON, T-2 and 3-ADON could induce chromosome aberrations in V79 cells starting from 1 ng/ml-a very low concentration. When concentrations increased to certain range they all showed toxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cardia; Esophageal Neoplasms; Humans; Mycotoxins; Sesquiterpenes; Stomach Neoplasms; Trichothecenes; Zea mays; Zearalenone