Study Of The Mechanism Of Cadmium Induced Renal Cancer Progression

Background:Kidney cancer has been gradually increasing over the last two decades.Advances in medical imaging modalities are not the only reason for these increases.Cadmium(Cd),a natural environmental pollutant that accumulates in the renal cortex and causes chronic kidney disease,is noted to be a key carcinogen of major concern.The conventional understanding previously was that when cadmium mostly amasses in proximal tubule cells,it causes a number of fairly nonspecific toxic effects that cause renal epithelial cells to die through necrosis or apoptosis.Nonetheless,there is an increasing evidence that the primary phases of cadmium-induced proximal tubule damage include not only cellular death,but also cell-cell adhesion,cell signaling mechanisms,as well as more specific changes in autophagy.These toxic effects observed before the occurrence of necrosis and apoptosis indicate that cadmium can be the basis of renal cancer.The effect of low-dose of cadmium has been evaluated in renal cancer.However,the impact of Cd in the development of renal tumor is still unknown.The objective of this research is to determine how low-dose Cd exposure affects renal cancer cells and to ascertain its mechanism that defines it.Methodology In this study,Caki-1,786-O,and 769-P cell lines were subject to investigate the pathogenic mechanisms related to cadmium-induced renal cancer.Cadmium’s effects on renal cancer cells at low doses on cell viability,cytotoxicity,and migration were studied.In addition,the functions of reactive oxygen species(ROS),effects of COX2 catalytic product prostaglandin E2(PGE2),Ca2+ and cyclic AMP(cAMP)/protein kinase A(PKA)cyclooxygenase 2(COX2)signaling on the invasion and migration of were all studied.Results:The results indicated that,low-dose Cd exposure advanced renal cancer Caki-1 cells,migration,which was independent of Cd-induced ROS and intracellular Ca2+ levels.Exposure of Cd,induced cAMP/PKA-COX2,which facilitated invasion and migration of cell,whiles decreasing the expressions of epithelial-mesenchymal transition(EMT)maker and E-cadherin,but the protein expressions of Vimentin and N-cadherin expressions increased.Similarly,when cAMP/PKA-COX2 signal is activated,it resulted the feedback secretion of PGE2 induced by cadmium.It also promoted EMT,migration and invasion of renal cancer line Caki-1.Conclusion:The findings of this study support the outcome of low-dose Cd exposure on the development of renal cancer cells and the mechanism that underpins it.The outcome of this research indicates that low-dose Cd exposure enhances invasion and migration of cell,and that it is due to Cd-activated cAMP/PKA-COX2 signaling.In addition,Cd induces migration of renal cancer cell and invasion by inducing the secretion and synthesis of PGE2,which feeds back cAMP/PKA-COX2 signals.