Our

experiment aimed to identify which drug-resistant selleck chemicals cell line is the ideal model for the study of the mechanism of hepatoma drug-resistance and paves a way for the further investigation of drug-resistant and its reversal. Comparisons of three drug-resistance models The induction of multi-drug resistance in tumor cells was caused by factors such as P-gp [9], MRP, LRP, GST, glutathione, glutathione S-transferase, protein kinase C, apoptosis-related gene (bcl-2, c-myc, p53), and the high-expression of GCS in the cancer cell living environment and variation of DNA type II topoisomerase activity [10–17]. As the drug-resistant mechanism of tumors is quite complicated, the drug-resistant phenotype of MDR cells was contained in cell specificity, distinct inductive medicines and diverse induction methods, the concluded drug-resistant phenotype was not quite uniform [18–20]. In our experiment, we compared three types PP2 supplier of multi-drug resistant human

hepatocellular carcinoma cell sub-lines ADM model established by three methods. The summary is shown below. Comparisons of biological characteristics in the three models The morphology of each drug-resistant cell line was irregular, volume was slightly increased compared with the parental generation, growth velocity was slower which enables accumulative growth, cell boundaries were obscure, massive particles and vacuoles were observed in the cytoplasm, and a slight shrinkage of the nucleus appeared. The in vitro induction of drug-resistant cells showed significant differences and the morphology of drug-resistant cell induced by in vivo implantation was close to the parental generation. The doubling times of the three drug-resistant cell lines, which were significantly extended compared with the parent cell line, revealed that growth velocity and the reproductive activity of the

drug-resistant cell line applied by an in vitro concentration gradient incremental method was significantly lower than that of the other two kinds of in vivo inductions. For the mechanisms of drug-resistance, the higher increase of drug excretion induced by a drug efflux pump was one of the most common drug-resistant reactions [21]. For this reason, we detected and compared the influx and efflux of ADM in three kinds of cells. Org 27569 The results indicated that the efflux rates of the four MK 8931 groups were 34.14%, 61.56%, 66.56% and 81.06%. Efflux rate of ADM by the resistant cell was significantly increased which was reflected as the drug stagnation diminished. This caused the intracellular drug concentration to decrease and diminish the impairment of cell target organs by drugs, which is presumed to be the main cause of the higher drug-resistant index. Expressions of P-gp and MRP in the three groups of drug-resistant cells were significantly increased compared with the parental generation. The expression of GSH/GST in the three groups showed no statistical significance by paired comparison (P > 0.05).

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