The Research About Increasing Autophagy In HCC

Background & Objective:Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in southern China, Taiwan, southeastern Asia, and sub-Saharan Africa. The overall survival (OS) of HCC patients remains poor despite improved diagnostic and treatment strategies. Indeed, HCC is a type of cancer highly resistant to conventional antineoplastic medicines, hich is partially attributed to the property of insensitivity to cell death induced by cytotoxic agents. It is well known that the avoidance of apoptosis is one of the hallmarks of cancer cells and that failure to induce apoptosis by anticancer treatments contributes to chemo- therapeutic failure and tumor progression. However, the role of autophagy, an alternative caspase-independent cell death program, and its underlying molecular mechanism, is still controversial in cancer, especially in tumor progression.Autophagy is the degradation of redundant or faulty cell components. It occurs as part of a cell's everyday activities and as a response to stressful stimuli, such as starvation. Auto- phagy can be divided into 3 types: macroautophagy, microautophagy, and chaperone- mediated autophagy. Several key autophagy genes are important to the initiation and regulation of autophagy, such as Beclin-1. Human beclin 1 is the first identified mammalian gene to induce autophagy. It is commonly expressed at reduced levels in ovarian tumors,breast tumors and prostatic tumors; however, there is no final conclution about status of autophagy and expression of Beclin-1 in hepatocellular carcinoma. Some authors reported the reduction of autophagy might facilitate tumor malignant differentiation, which results in a more aggressive cancer cell phenotype and poor prognosis of HCC. After collecting a lot of tissue HCC and taking electron microscope pictures, we find the phenomenon of increasing autophagy in HCC. To expose the possible mechanism and biological significance of increasing autophagy and up-regulation of beclin-1 protein, we investigated the regulation of beclin1 expression and observe the phenomenon of autophagy in HCC tissues.Materials & Methods:The sections of 54 HCC tissues were collected from the East Hepatobiliary Hospital affiliated to Second Military Medical University during the year of 2006-2007. HCC patients were 45 males and 9 females, with a mean age of 50.2 years(range, 17-70 years). The Edmonson staging of these patients was based on the clinical and pathological diagnosis. Informed consent was obtained from each patient before operation. The status of autophagy in the samples was observed through electron microscope and expression of autophagy in the samples was detected by Western blotting and.immunohistochemical staining, and investigated the regulation of beclin1 expression in cell lines, moreover, we took statistical analysis to clinic data by SPSS software.Conclusions:1. The status of Autophagy in HCC tissue was strongly conspicuous,. the expression of Beclin-1 was up-regulate in HCC tissue,but it is different in normal hepatic tissue and cholangiocarcinoma tissue.2.The HBx protein can increase the expression of Beclin-1 in cytoplasm, moreover, it can impare chondriosome in cell, we think that disfunction of autophagy is not one of primary point of hepatocarcinogenesis; status of autophagy may be related to extent of impared mitochondria in hepatitis B virus (HBV)-infected cancerous liver tissues.3.We find there were a lot of cytolysosome in normal cell next tumor cell, we think them are microautophagy, and we find rough endoplasmic reticulum can construct the membrame of macro autophagosome.4. The extent of expression of Beclin-1 in HCC is probably correlated to the size of tumors and patient's condition.