Background: Dysregulation of apoptotic pathway plays a critical role in tumor progression and resistance to chemo-, immuno- and radio-therapy in human renal cell carcinoma (RCC). The X-linked Inhibitor of Apoptosis (XIAP), a key member of the Inhibitors of Apoptosis Protein (IAP) family, possesses the most potential to inhibit apoptosis by directly binding the initiator caspase-9, -3 and -7, thereby promoting tumor cell survival during tumor progression and numerous anticancer therapies.
Methods: We investigated the difference of XIAP basal expression level and evaluated its contribution to the resistance to apoptosis in RCC cell lines exposed to apoptosis-inducing drugs by histological methods and western blot analysis, than through RNAi, we got down-regulation XIAP expression clone no.2 cells, and observed its contribution to the sensitivity to apoptosis induced through Intrinsic pathway.
Results: The different levels of XIAP expression could be detected in RCC cell lines between ClearCa-2 and ClearCa-6. CleraCa-6 with lower expression of XIAP much more sensitive to the apoptotic induced by means of death receptor and mitochondria pathway and NF-κB inhibition than ClearCa-2 with higher expression of XIAP(P<0.05). Downregulation of XIAP expression was observed in both cell lines by NF-κB inhibitor and in ClearCa-6 by the apoptotic induction mediated by mitochondria pathway. However, there existed the observed different levels of XIAP expression in ClearCa-2 and ClearCa-6 cell lines all along during the apoptotic inductions. Further, no-expression of XIAP cell line-clone no.2 was transfected, and it was more sensitive to the apoptosis inductions by mitochondria pathway.
Conclusions: Our result suggests that down-regulation XIAP expression can enhance the sensitivity of RCC cells to apoptosis, and the basal expression of XIAP in apoptosis process is stable. And this may provide reliable evidence and new ideas for targeted against XIAP gene therapy in clinical mentioned.
