Targeted systemic therapies to treat HCC patients with advanced stages had become one of urgent needs in the management of HCC. Hepatocellular carcinoma (HCC) accounts for around 85-95% of all PLC cases. Primary liver cancer is one of the most common cancers in the world and the third cause of cancer-related death. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors. Our results suggest a correlation of ABCG2 gene expression and differentiation stage both in human and HCC derived cell lines. This up-regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4 than in well-differentiated G1/G2 HCC. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. The gene expression was also investigated in 51 adult liver tissues with HCC and related cirrhosis normal liver tissue was used as control. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (p<0.01). ResultsĪBCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay protein content was assessed by SDS-PAGE Western blot. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy. The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance.
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