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Glutathione S-transferase (GSTπ), one of the phase Ⅱ detoxification enzymes, is usually over-expressed in many human tumors. It displays a key role in protecting cells through catalyzing the conjugation of glutathione (GSH) with a broad range of electrophilic substrates including chemotherapeutic agents. As the above conjugates can be effluxed from cells easily, the efficacy of various chemotherapeutic agents is reduced. Recent studies suggest that GSTπ also plays an important role in inhibiting apoptosis through blocking the JNK signaling pathway. In this way, GSTπ protects cells from apoptosis. Therefore, GSTπ has become an attractive target against cancers, especially for drug-resistant tumors. A great deal of effort has been devoted to the discovery of GSTπ inhibitors and prodrugs over the last decade. In connection with authors' current research, we provide a review on studies on progress of GSTπ inhibitors and prodrugs along with the future strategies.
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Objective To explore the expressions of Topo-Ⅱ,GST-π in gastric cancer tissues and normal gastric mucosa tissues,to reveal its relationship with clinical pathological features and significance.Methods Immunohistochemical method was used to detect Topo-Ⅱ,GST-π expressions in 100 cases of gastric carcinoma and 20 cases of normal gastric mucosa,make a comprehensive analysis combined with clinical pathology data.Results There were significant difference of expression of Topo-Ⅱ,GST-π between the normal gastric mucosa tissues and gastric cancer of different degree of differentiation.Topo-Ⅱ positive expression rate of 5.0 ％ (1/20),100 ％ (30/30),96.7 ％ (29/30) and 87.5 ％ (35/40) respectively; GST-π positive expression rate were 60.0 ％ (12/20),83.3 ％ (24/30),96.7 ％ (29/30) and 100.0 ％ (40/40) respectively (P ＜ 0.05).The expressions of Topo-Ⅱ,GST-π in gastric cancer tissue were not relevant to patient' s sex,age,tumor location,infiltration depth (P ＞ 0.05).Topo-Ⅱ associated with the differentiation degree and lymph node metastasis of tumors,with the decreasing degree of tumor differentiation,lymph node metastasis,Topo-Ⅱ expression also decreased.GST-π was associated with tumor diameter,degree of differentiation and lymph node metastasis,the lower the degree of differentiation,lymph node metastasis,tumor diameter the more,GST-π expression increased (P ＜ 0.05).GST-π and Topo-Ⅱ were negative correlation and both expressed in gastric cancer tissue (P ＜ 0.01).Conclusions The expressions of Topo-Ⅱ in gastric cancer tissue is associated with the differentiation degree and lymph node metastasis of the tumor.GST-π is associated with tumor diameter,the degree of differentiation and lymph node metastasis.GST-π and Topo-Ⅱ in gastric cancer tissues are negatively correlated.
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Objective To explore the expression of glutathione-S-transferase-π(GST-π),P-glycoprotein (P-gp),topoisomerase Ⅱ (Topo Ⅱ) and thymidylate synthase (TS) in gastric adenocarcinoma tissues and the clinical significance.Methods Envision method of immunohistochemistry was used to detect the expression of GST-π,P-gp,Topo Ⅱ and TS in sample of 64 gastric adenocarcinoma tissues and 12 normal gastric mucosas,and their corresponding clinical data were comprehensive analyzed.Results The expression positive rates of GST-π,P-gp,Topo Ⅱand TS were respectively 76.6 ％(49/64),64.1％ (41/64),84.4 ％ (50/64) and 53.1％ (34/64),that were all higher than in gastric mucosa [8.3 ％ (1/12),8.3 ％(1/12),16.7 ％ (2/12),0],the differences were statistically significant respectively (P ＜ 0.01).Their positive expression rates were closely relevant to the degree of differentiation (P ＜ 0.05),but not to the patients' gender,age,tumour size,clinical staging,invasive depth and lymph node metastasis (P ＞ 0.05).The expressions of GST-π,P-gp and TS in high and middle differentiation adenocarcinoma were high.er than in low differentiation,but the expression of Topo Ⅱ in high and middle differentiation adenocarcinoma was lower than in low differentiation (P ＜ 0.05).Conclusion GST-π,P-gp,Topo Ⅱ and TS are over-expressed in gastric adenocarcinoma,which is related to the multidrug resistance of gastric adenocarcinoma.The joint detection of the expression of GST-π,P-gp,Topo Ⅱ and TS in gastric adenocarcinoma can be looked as an important symbol for guiding its chemotherapy drug and prognosis.
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Objective: To investigate the anti-apoptosis competence and the expression of glutathione- S-transferase-π (GST-π) of tumor spheres from lung cancer cell line A549. Methods: The tumor spheres were achieved from lung cancer cell line A549 cultured in serum-free medium. The apoptosis rates of both tumor spheres and primary A549 cells after treatment with cisplatin were detected by immunofluorescence assay with Annexin V-FITC+PI and JC-1 stainings, and the expressions of GST-π protein were also examined in the tumor spheres and the primary A549 cells as well as their grafted tumors in nude mice by Western blotting and fluorescence immunohistochemistry, respectively. Results: Immunofluorescence assay showed that the apoptosis rate was significantly higher in tumor spheres than that in primary A549 cells. Compared with the primary A549 cells and their corresponding grafted tumors, the expression levels of GST-π protein were significantly higher in the tumor spheres and their corresponding grafted tumors. Conclusion: Tumor spheres from lung cancer cell line A549 have a strong capability of drug-resistance, which is probably associated with the up-regulated expressions of drug-resistance proteins in these tumor spheres.
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Objective To investigate the expression of muhidrug resistance-related protein 1 (MRP1),lung resistance-related protein(LfuP)and glutathione S-transferase-π(GST-π)in carcinoma of the gallbladder and cholangiocarcinoma. Methoils MRP1,LRP,GST-πwere measured in experimental group(18 cases of carcinoma of the gallbladder,36 CSSeS Of cholangiocarcinoma)and control group(13cases of cholecystitis and cholangeitis)by immunohistochemistry.Statistical analysis used chi-square test and spearman test. Results The positive rate of MRP1,LRP,GST-π in carcinoma of the gallbladder and eholangiocarcinoma were 72%(13/18),78%(14/18),61%(11/18)and 86%(31/36),75%(27/36),69%(25/36),respectively,significantly higher than those of 23%(3/13),23%(3/13),23%(3/13)(X2=4.5,P＜0.05)in control group.The expression of LRP[93%(13/14)]in pafients＞60 years old was significantly higher than 64%(14/22)in patients younger than 60 yrs old(x2=3.9,P ＜0.05).In addition,their expression was not related to gender,age,staging,tumor differentiation and lymph node metastasis(P＞0.05).The expression of MRP1 was related with tllose Of GST-π,Spearman correlation coefficient=0.569(P＜0.05).Conclusions MRP1,LRP,GsT-π were over expressed in various degrees in carcinoma Of the gallbladder and cholangiocarcinoma witllout chemotherapy.and related to the primary muhidrug resistance Of cholangiocarcinoma and carcinoma of the gallbladder.