Aldose reductase (AR) is an aldehyde and carbohydrate compounds reductase, NADPH as a coenzyme, can restore the natural or in vivo metabolism of toxic aldehydes such as glyceraldehyde, three-deoxyglucose ketone aldehyde AR is the starting enzyme of glucose metabolism sorbitol bypass and a key enzyme in the catalytic conversion of glucose to sorbitol. The relationship found between the AR gene and liver cancer, the AR gene is expressed at high levels in human and rat hepatoma tissues, very low level of expression in normal liver tissues. Found a new gene with a gene encoding amino acid sequence homology, named for the gene of the ADP-ribosylation factor-like 11. The gene is expressed at high levels in 54% of primary liver cancer, but is undetectable in normal liver tissue expression,
ARL11 and AR enzyme activity and substrate range. The study found that HepG2 cells transfer dye ARL11, high expression of ARL11 protein in HepG2 genetically modified cells to certain anticancer drugs with aldehyde, such as doxorubicin, mitomycin resistance enhanced.Tumor cell resistance to chemotherapeutic drugs is the main reason for the failure of chemotherapy, the study found that drug resistance and molecular mechanisms are complex, the current study is mainly concentrated in the multidrug resistance gene abnormal expression of proto-oncogene expression abnormalities and DNA damage repair gene expression abnormalities.
Reported in the literature, the high expression of the aldose reductase (AR) in hepatocellular carcinoma, hypertonic HepG2 cells induced by high expression of AR enhanced cell resistance to anticancer drugs on aldehyde, suggesting its possible liver cancer is resistant to certain drugs One of the reasons. ARL11 and AR enzyme activity and substrate range of cytotoxic compounds containing carbon acyl, aldehyde group-containing aromatic compounds and aliphatic compounds have a strong reduction of the gene is highly expressed in the small intestine and colon, suggesting that its physiological function may restore the body's toxic aldehyde compounds. ARL11 and AR expression in hepatoma cells to accelerate the detoxification of a variety of toxic aldehydes and carbonyl acid compounds, which may promote the sustained growth of cancer cells.HepG2 cells express low levels of ARL11, through gene transfection, a stable high expression of ARL11 gene cells. Study found that liver cancer cells may be due to high expression of ARL11 containing aldehyde group of anticancer drugs, such as ADM, MMC, is not sensitive. ARL11 gene have a higher specificity than the AR gene expression in hepatocellular carcinoma, containing the aldehyde group of anticancer drugs have a stronger resistance, so we speculated that the relationship between ARL11 and liver cancer drug resistance could have important implications . High expression of the gene ARL11 cell line will provide a convenient, fast tool screening sensitivity of anticancer drugs. The ARL11 specific expression in hepatoma cells may be used as both indicators of liver cancer early diagnosis, but also can be used as explore new targeted therapy for liver cancer prodrug way.
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