The Expression Of Glucosylceramide Synthase In Human Hepatocellular Carcinoma And Its Relationship With The Expressions Of Multidrug Resistance-related Proteins

Objective To study the expression of glucosylceramide synthase(GCS) and its relationship with the expressions of P-glycoprotein(P-gp),glutathione S-transferase pi(GST-π) and DNA topoisomeraseⅡ(Topo-Ⅱ) in human hepatocellular carcinoma(HCC).Methods The expression of GCS,P-gp,GST-πand Topo-Ⅱin 49cases with HCC,14 cases with cirrhosis and 14 cases with normal tissue were detected by immunohistochemical technique S-P(streptavidin- biotin peroxidase method).Results1.The staining of GCS was mainly located in the cytoplasma.The expressions in HCC,cirrhosis and normal liver tissue was 91.84%(34/49),71.43%(10/14),21.43%(3/14),respectively.There was significant difference in HCC,cirrhosis and normal liver(P＜0.05).The positive expression rate of GCS in HCC was significantly higher than that in normal liver tissue(P＜0.017).No significant difference was seen between HCC and cirrhosis and no significant difference was seen between cirrhosis and normal liver tissue(P＞0.017).The positive expression rate of GCS was significantly correlated with tumor mass in HCC(P＜0.05),which was 85.71%(12/14) in tumor mass＜5 cm and 42.86%(15/35) in those≥5 cm.2.The staining of P-gp was mainly located in membrance.The expressions in HCC, cirrhosis,and normal liver were 61.22%(30/49),28.57%(4/14),21.43%(3/14),respectively.There were significant difference in HCC,cirrhosis and normal liver (P＜0.05).Those were higher in HCC than in cirrhosis and normal liver(P＜0.017).No significant difference was seen between cirrhosis and normal liver(P＞0.05).The positive expression was no correlated with patients' clinical-pathological parameters.3.The staining of GST-n was mainly located in cytoplasma.The expressions in HCC,cirrhosis,and normal liver were 77.55%(38/49),14.29%(2/14),21.43%(3/14), respectively.There were significant difference in HCC,cirrhosis and normal liver (P＜0.05).In the area of HCC,the expressions were significant higher than those in cirrhosis and normal liver(P＜0.017).No significant difference was seen between cirrhosis and normal liver(P＞0.05).The positive expression was no correlated with patients' clinical-pathological parameters.4 The staining of Topo-Ⅱwas detected in 16 of 49(32.65%)HCC.There was no positive expression in cirrhosis or in normal tissues,positive expression was mainly in cell nucleolus.There were significant difference in HCC,cirrhosis and normal liver (P＜0.05).The positive expression rate of Topo-Ⅱwas significantly correlated with Edmondson's grade and metastasis(P＜0.05),which was 5.8%in Edmondson's gradeⅠ/Ⅱ,46.88%in gradeⅢ/Ⅳ,70%in metastasis and 23.08%in no metastasis,respectively。5.The positve relationship between the expression of GCS and P-gp(r=0.261, P＜0.05),GST-π(r=0.531,P＜0.001)and Topo-Ⅱ(r=0.295,P＜0.01) could be found with statistical significance.6 The positive relationship between the expression of P-gp and GST-πcould be found with statistical significance(r=0.323,P＜0.05).Conclusions1.Enhanced glucosylceramide synthase was seen in HCC,which may controbute to multidrug resistance.GCS could be a potential target for treatment of HCC.2.The expression of GCS is closely co-related to those of P-gp,GST-πand Topo-Ⅱin HCC.Some connection between them in the course of HCC multidrug resistance is suggested.3.The co-increased expressions of GCS and those multidrug resistance-related proteins might be the result of some common up-regulated gene products.