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Objective To investigate the mRNA expression of the multidrug resistance associated protein and lung resistance protein in human non-small cell lung cancer tissues and their relationship with cis-platinum. Methods 13 samples were collected from patients with non small cell lung cancer before and after chemotherapy, the mRNA expression of MRP and LRP were detected using RT-PCR method, correlation between two genes were studied by Logistic regression analysis. Results Compared with before cisplatin chemotherapy, MRP and LRP expression of patients were increased after chemotherapy(P<0.05).Logistic regression analysis showed that there is no correlation between the two genes(r=0.036,P<0.05). Conclusion Cisplatin chemotherapy can increase the mRNA expression of MRP and LRP, and there is no correlation between the two genes.
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Objective: To investigate the relationship between the c-Jun N-terminal kinase (JNK) pathway and lung-resistance protein (LRP). Methods:A549 cells were treated with various concentrations of CDDP for 72 h. The LRP mRNA expression was then analyzed using reverse transcription PCR (RT-PCR). LRP, JNK, and P-JNK were analyzed by Western blotting. The A549 cells were then pretreated with SP600125 (2 μg/ml to 4 μg/ml ) for 1 h. Afterward, CDDP (16 μg/ml) was added into the culture for 72 h. A Cell Counting Kit-8 was used to investigate the sensitivity of CDDP to the A549 cells. Flow cytometry was used to detect the apoptosis rate. The LRP mRNA expression was analyzed using RT-PCR. LRP, JNK, and P-JNK were analyzed by Western blotting. Results:CDDP in-duced the mRNA and protein expression of both LRP and P-JNK in a dose-dependent manner. Pretreatment with SP600125 enhanced the sensitivity of CDDP to the A549 cells and increased the apoptosis rate. However, the LRP mRNA and LRP expression in the pre-treated cells was lower than that in the presence of CDDP alone. Conclusion:In A549 cells, CDDP induces the LRP expression via the JNK pathway. This result suggests that lung cancer therapy can be improved by the addition of CDDP to inhibit the JNK signaling path-way.
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Objective To detect the expression of multidrug resistance proteins P-gp, LRP, MRP, and analyze the relationship between them and the clinicopathological factors. Methods The expression of P-gp,LRP, MRP in formalin-fixed paraffin-embedded tissue sections was determined by a labelled StreptavidinPeroxidase (SP) immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery. Results The positive rates of P-gp, LRP, MRP were 86.4 %, 84.7 % and 27.1%, respectively. The difference between the positive rate of P-gp and MRP was significant statistically, as well as the difference between the expression of MRP and LRP. No significant difference was observed between P-gp and LRP, but the positively correlation between the expression of P-gp and LRP was observed. No significant correlation between the expression of P-gp, LRP, MRP and the grade of differentiation were observed. The expression of P-gp was correlated with clinical stages positively (r=0.742), but the difference with the expression of P-gp in different stages was not significant. Conclusion The expression of P-gp, LRP, MRP in patients with gastric cancer without prior chemotherapy are high and indicates that innate drug resistance may exist in gastric cancer.
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Lung resistance protein (LRP) is a gene which is found early and is closely related to multidrug resistance. LRP is expressed in most normal tissues with secretory function and is involved in secretion and cell detoxification function. LRP can also be seen expressed in malignant tumors including gastric cancer. There is a certain correlation between LRP expression and the prognosis of malignant tumor patients. LRP plays the role of multi-drug resistance mainly by preventing chemotherapy drugs into the nucleus and pumping chemother apy drugs out of the cells.
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The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.
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Middle Aged , Male , Infant , Humans , Female , Child, Preschool , Child , Aged , Adult , Adolescent , Vault Ribonucleoprotein Particles/genetics , Survival Rate , RNA, Neoplasm/genetics , RNA, Messenger/genetics , Prognosis , Neoplasm Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Leukemia/drug therapy , Genes, MDR , Gene Expression , Base SequenceABSTRACT
Objective To explore the effect of different doses of cyclophosphamide(CTX) on the drug-resistance of implanted human A549 lung cancer in nude mice,and investigate the anti-tumor effect and toxicity.Methods BALB/c nude mice bearing A549 lung carcinoma were randomized into low-dose metronomic(LDM) CTX group,maximum tolerate dose(MTD) CTX group and normal saline group.The changes of tumor volume,weight and toxicity were observed.Expression of glutathione S-transferase-?(GST-?) and lung resistance-related protein(LRP) in the tumor were detected by immunohistochemistry SP method.Results In LDM CTX group,the tumor grew fast at first,then slowed down gradually and grew slowly for a long time,while in MTD CTX group tumor grew slowly at first,then it accelerated.Side effects of chemotherapy:the weight of nude mice was lost persistently in MTD CTX group,while lost insignificantly in LDM CTX group.No obvious toxicity was observed in LDM CTX group.GST-? and LRP expression in LDM CTX group were not significantly different from those in the control,but significance was seen in MTD CTX group compared with those in the control(P
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Objective:To study the expression and clinical significance of MRP and LRP in carcinoma of large intestine.Methods:Immunohistochemistry is used to examine the MRP and LRP expression in 60 cases of large intestine carcinoma and 10 cases of normal large intestine tissues.Results:The positive expression rates of MRP and LRP in the 60 cases of large intestine carcinoma are 68.3% and 70% respectively and are all significantly higher than those in normal large intestine tissues ( P 0.05).Conclusion:MRP and LRP are both highly expressed in large intestine carcinoma and play an important role in the primary multidrug resistence(MDR) of large intestine carcinoma.
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0.05).The patients with positive P gp and LRP expression responded more poorly to chemotherapy than those with negative P gp and LRP expression ( P
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Objective To study the expressions and significance of MRP and LRP in HCC. Methods The expressions of two genes were examined in three tissues (54 cases of HCC, 24 para cancer and 12 posthepatitis cirrhosis tissues) by SP immunohistochemical and PCR techniques. Results MRP and LRP were expressed in three tissues, with significantly higher rates in HCC than others (P
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Multidrug resistance (MDR) is widely thought to be a major cause of the failure in cancer chemotherapy. The detection of MDR marker is therefore valuabe in studying the mechanisms of MDR and to predict response to chemotherapy in patient with carcinoma. Previous studies have examined MDR marker in gastric cancer, but the major part of the investigation in patients have focused on a single parameter. The purposes of this study were to detect the expression of glutathione S transferase pi(GST ?), multidrug resistance associated protein(MRP), lung resistance protein(LRP) and multidrug resistance gen 1 (MDR1) in the patients with primary gastric cancer, who had not received prior chemotherapy, and evaluate the correlation between GST ?, MRP, LRP and MDR1. The expression of GST ?, MRP, LRP and MDR1 mRNA in carcinoma tissue and the adjacent non cancerous tissue from 50 patients was examined by semiquantitative reverse transcription polymerase chain reaction (RT PCR). The positive rate of GST ? mRNA, MRP mRNA, LRP mRNA and MDR1 mRNA in gastric cancer tissue were 36.00%, 12.00%, 10.00%, and 10.00% respectively. Their expression in gastric cancer tissue was significantly higher than that in the adjacent non cancerous tissue. The overall positive rate of their expression in gastric tissue was 48.00%. The results indicated that GST ? mRNA, MRP mRNA, LRP mRNA and MDR1 mRNA are overexpressed in various degrees and no co expression exists among the studied genes in gastric cancer,and perhaps intrinsic MDR exists in 46% patients with primary gastric cancer .