| Objective:After the IHC assay of the protein expression of lung resistance protein(LRP) and glutathione-s-transferaseπ(GST-π) and the drug resistances assessment of 6 common antitumor medication in-vitro with fresh tumor cell culture in human brain gliomas,①the corelation between the protein expression of LRP and GST-π,②the relation of these protein expression with the pathological grades of gliomas,③the relation among the drug sensitivity of six antitumor chemotherapeutic drugs of brain glioma cultures,④the relationship of the drug resistance and the pathological grades of gliomas, and⑤the relation between the protein expression and the drug resistances were explored as to study the role of the expression of PRL and GST-πon the antitumor drug resistance of chemotherapy in human gliomas. The findings can provide some laboratory research data to estimate the prognosis of glioma patients and detect the drug resistance varieties as to develop the individualized treatment strategies for each patient and avoid ineffective drugs admission. This can be helpful in the guidance of rational clinical application of antitumor drugs, and ultimately improve the long-term outcome of glioma patients.Methods:There were 27 in-patient glioma cases in the department of neurosurgery, Sichuan provincial people's Hospital between May 2010 and April 2011 were enrolled in the study. All of the fresh tumor specimens were sent to the following assays as①the common pathological and IHC study,②the protein expression of GST-πand LRP in IHC,③the in vitro antitumor drug resistance in primary glioma cell culture. The sterile tumor tissue was used to culture primary tumor cell for sufficient single cell suspension. Then drug sensitivity experiment was implemented under the antitumor drugs-peak plasma concentration (1*PPC) of 6 common used chemotherapeutic drugs for 72 hours. Through the MTT assay the survival tumor cell were measured and the inhibitory rates were calculated there after. There were 7 normal brain tissues, which came from the removal tissues of decompression in severe head injury patients, as a comparison. The pathological and IHC assay were done in these cases. And the SPSS 13.0 statistical software was used to analysis the data of this study.Results:1. The expressions of the GST-πand LRP in human gliomas:The positive expression rate of GST-πin human glioma was 66.67%(18/27). And in normal brain tissues, the positive expression of GST-πwas 0%(0/7). The difference between them were significant statistically(χ2=9.265, P=0.002). The positive rate of LRP expression in human glioma was 55.56%(16/27). In normal brain tissues, the positive rate of LRP expression was 0%(0/7). The difference between them were statistically significant (χ2=7.368, P=0.007). The positive rate of GST-πand LRP expression among patients of different pathological grades existed positive correlation (R=0.735,0.553; P=0.000, 0.003). Yet there was no correlation between the positive rate of GST-πand LRP expression in human gliom a(R=-0.012, P=0.954).2. The in vitro drug sensitivity of brain gliomas:The drug resistance assay was succeeded in all 27 cases. Take the tumor cell inhibitory rate of 30% or more as sensitive. Twenty-four of 27 specimens showed positive of sensitivity in one drug or more. The sensitivity sequence of six chemotherapeutic drugs from high to low was VM-26 (20/27), ACNU (18/27), TMZ (16/27), BCNU (15/27), DDP (11/27) and VCR (6/27). There was significant difference between the sensitivity of different chemotherapeutic drugs (X2=19.234, P=0.002). And there was a negative correlation between the drug sensitivity and the tumor pathological grades (X2=19.234, P=0.002).3. The corelation between the expression of GST-πand LRP in human glioma and the resistance of antitumor drugs:The statistic analysis of the experiment results show that the positive expression of GST-πand LRP were in negative relationship with the inhibitory rate of antitumor drugs as shown in the table. And the relationship was statistically significant between GST-πand VM-26, ACCU, TMZ and BCN. And the relationship was statistically significant between LRP and VM-26, TMZ, BCNU, DDP and VCR also. Conclusion:1. GST-πand LRP expression were commonly observed in human glioma tissue. The expression is in positive relation with the gloima pathological grades. And the high expression of GST-πand LRP indicate the high drug resistance.2. There were positive in vitro drug resisitance in all 6 common antitumor drugs in this study. The sensitivity varied among different drugs and different pathological grades of gliomas. The sensitivity sequence of drugs were as follows VM-26> ACNU> TMZ> BCNU> DDP> VCR. The drug sensitivity was in negative relation with the pathological grades of gliomas. High grade glioma indicates low sensitivity and high resistance.3. There may be a close relationship between the expression of GST-πand LRP in human glioma and the in vitro resistance of antitumor drugs. The high expression of GST-πand LRP and high resistance may indicate poor outcome of glioma.4. The combined assay of the biological features may play an important role in the personalized therapeutic of brain glioma: The high expression level of GST-πand LRP in human glioma, detected by the IHC technique, may serve as an important indicator of drug resistance. The combined in vitro chemosensitivity assay can give more information for the clinics. All this data can help the optimized choice of rational drugs, increase the purpose and efficacy of clinical chemotherapy, and ultimately avoid the ineffective treatment and reduce the unnecessary side effects and economic burden on patients.5. Therefore, targeted suppression of GST-πand LRP expression in human glioma cell could represent a novel approach to comprehensive, effective treatment of human glioma in the future. |
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