Autophagy Is Activated In Cholangiocellular Carcinoma: It's Inhibition Leads To Cell Apoptosis And Enhances Chemotherapy Sensitivity

Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor which arises from the epithelial cells of intrahepatic bile ducts (beyond the second order bile ducts). The incidence of ICC is reported to be about 10% of primary liver cancers and its lethality is also on the top of primary liver cancers. Chronic cholangitis, HCV/HBV infection, choledochal cysts etal are significantly associated with ICC. ICC has the worst prognosis of any tumor arising in the liver; its 5-year survival is poor, and accompanied by a high recurrence rate. The overall 5-year survival rate ranges 15%-20%. The development and progression of ICC is a complicated process involving multiple genes and transforming steps. But the mechanisms underlying the development of ICC remain unclear. Therefore, searching for new ICC associated molecules may broaden our view to the progress of ICC.Autophagy occurs when cells need to'selfcannibalize'or degrade their constituents. Underlying'housekeeping'levels of autophagy probably occur in most normal cells to prevent the accumulation of protein aggregates and defective cellular substructures. Certain environmental cues (such as starvation, high temperature, low oxygen, hormonal stimulation) or intracellular stress (damaged organelles, accumulation of mutant proteins, microbial invasion) activate signalling pathways that increase autophagy. Inactivation of autophagy-specific genes, such as beclin 1, results in increased tumorigenesis in mice, and enforced expression of such genes (beclin 1, atg5) inhibits the formation of human breast tumours in mouse models. Some researches show that in cancer cells, metabolic stress robustly induces autophagy, which is sustained when apoptosis is blocked. And it is essential for cell's survival during starvation. Either indirectly by inhibitors or directly by allelic loss of Beclinl or deficiency in Atg5, or by RNA interference (RNAi), prevents survival in response to metabolic deprivation. This research aimed at the expression level and its function of autophagy in ICC, as well as analyzed the correlation of the expression level of beclinl with the various clinicopathologic parameters by immunohistochemistry, and revealed the correlation of beclinl and cholangiocarcinoma prognosis.