PS02.049: HIGH GPX1 EXPRESSION PROMOTES ESOPHAGEAL SQUAMOUS CELL CARCINOMA INVASION, MIGRATION, PROLIFERATION AND CISPLATIN-RESISTANCE BUT CAN BE REDUCED BY VITAMIN D

Abstract

Abstract Background Esophageal cancer is one of the most common cancers worldwide. Despite recent progress in the devel- opment of novel therapies, esophageal carcinoma remains an aggressive cancer associated with a poor prognosis. The glutathione peroxidase 1 (GPX1) gene located on chromosome 3p21.3 is associated with the cancer of several organs. According to available information, GPX1, a gene downstream of NF-κB, is considered to exert adverse ef- fects on tumour progression and enhance malignancy in some cancers but has not been reported in esophageal cancer. It is also reported that vitamin D (Vit. D), a widely used drug in the clinical setting, could suppress GPX1 expression through the NF-κB pathway. Thus, it is speculated that Vit. D could reduce malignancy in esophageal cancer by altering the NF-κB pathway. Methods Selection GPX1 high expression EC109 and EC9706 cell line K150, and K180 low expression cell lines transfected with siRNA and vector. Using RT-PCR to detect cell transfection efficiency GPX1’s, Western blot detect the expression of uPA, MMP-2, NF-κB, and CCK-8 assay inhibition or overexpression on GPX1 on ESCC cell cisplatin resistance and proliferation. Transwell assay inhibition or over-expression of GPX1 on invasive ability of ESCC cells. Results By CCK-8 and transwell law found within the cells expressing low GPX1 ESCC can inhibit cell proliferation, cisplatin resistance, invasion and migration, high GPX1 when the opposite phenomenon can be observed. Western blot GPX1 down when found, PTEN, Bax activity rises, PDK-1, AKT, Bcl-2, uPA, MMP-2 expression decreased, vimentin, E-cadherin, ß-catenin, snail is no significant change. After Vit.D treatment, CCK-8 assay showed that cell proliferation and drug resistance was significantly inhibited; Transwell showed cell invasion and migration also decreased. Cells was detected by Western blot after transfection, cells, PTEN, Bax increased activity, p65, PDK-1, AKT, Bcl-2, uPA, MMP-2 expression decreased, vimentin, E-cadherin, ß-catenin, snail is no significant change. Conclusion Treatment with vitamin D can downregulate GPX1, thus decreasing tumour cell capacity for invasion, migration, proliferation and cisplatin resistance via the NF-κB pathway. Vitamin D, already commonly used in clinical therapy, could play a greater role in the treatment of esophageal cancer patients. Disclosure All authors have declared no conflicts of interest.