| Objective:To investigate the expressions of O6-methylguanine-DNA methyltransferase (MGMT) and DAN topoisomerase II alphassion (Topo-Ⅱ a) in human gliomas and the correlations between its expressions of the two proteins and the drug sensitivity of three kinds of common chemotherapeutics. The results of the experiment expectually provide rational and effectual conduct in the clinical personalized chemotherapy.Methods:We collected55fresh human glioma specimens which had been diagnosed glioma pathologically. The glioma tissues were taken in the neurosurgical operations and were sent to ordinary pathology, immunohistochemical detection the expression of MGMT and Topo-Ⅱ aprotein as well as in vitro drug sensitivity test simutaneously. The fresh tumor tissue of each patient was cut and digested to primary cultured tumor cell. MTT assay was used to detect the chemosensitivity of three common central nervous systematic chemotherapeutics as ACNU, TMZ and VM-26under the antitumor drugs-peak plasma concentration. And the statistical software SPSS17.0was utilized to analysis the correlation among the expression of MGMT and Topo-Ⅱ a and the chemosensitivity of the human brain glioma.Results:1. The expressions of MGMT and Topo-Ⅱ a in human brain gliomas:Significant difference (P<0.05) between gliomas and normal tissue were existed in the expression of the two protein. No correlations was found between the expression of MGMT and the pathological classification in gliomas (rs=0.072, P=0.063>0.05). The expression of Topo-Ⅱ a and pathological classification showed a significant inversive correlation (rs=-0.306, P=0.023<0.05)。2. Chemosensitivity of the human brain glioma asaay is as follows. The inhibilitation rate (IR) of three common used chemotherapeutics in the1*PPC in the human brain glioma cluture is variable. The IR>30%is defined as sensitive. There were27culture in ACNU group,30in TMZ and37in VM-36sensitive out of the55specimens. Statistic ananlysis showed P>0.05, that indicated no significant diference among the sensitivity of the three drugs.and there’s no difference between the sensitivity and the pathological classification.3. Correlations between the expression of MGMT and the drug sensitivity of three common chemotherapeutics:The inhibition ratio, which ACNU and TMZ acted on the gliomas culture, showed an inversive correlation to the expression of MGMT, rs of ACNU was-0.781, another was-0.761, the magnitude close to1, the probability of rs was below0.05. On the contrary, there was no correlation between the inhibition ratio of VM-26and the expression of MGMT, rs of VM-26was0.048, the magnitude close to0, the probability of rs was above0.05.4. Correlations between the expression of Topo-Ⅱa and the drug sensitivity of the three common chemotherapeutics:The inhibition ratio which VM-26acted on the gliomas culture showed a positive correlation to the expression of Topo-Ⅱa, rs of VM-26was0.825, the magnitude close to1, the probability of rs was below0.05. There was no correlations between the inhibition ratio of ACNU and TMZ and the expression of Topo-II a, rs of ACNU was-0.116, another was-0.015, the magnitude close to0, the probability of rs was above0.05.Conclusion:1. The expressions of MGMT and Topo-Ⅱ a in human brain gliomas. The expression of MGMT and Topo-Ⅱ a in human brain glioma was significant higher than that in normal brain tissues. The expression of MGMT was no relation to the pathological classification. However, the expression of Topo-Ⅱ a has an inversive correlation with the pathological classification. The expression of the two protein illustrated that there was obvious heterogeneity in gliomas or in the molecular biological targets of gliomas.2. Chemosensitivity of the human brain glioma culture is as follows. The IR was above30%in27from the ACNU group,30in TMZ and37in VM-26. Statistic ananlysis showed no significant diference among the sensitivity of the three drugs.and there’s no difference between the sensitivity and the pathological classification.3. Correlations among the expression of MGMT and Topo-Ⅱ a to the drug sensitivity of three common chemotherapeutics:The inhibition ratio of ACNU and TMZ in the gliomas culture had an inversive correlation to the expression of MGMT. That of VM-26showed a positive correlation to the expression of Topo-Ⅱ a. These are correspondant to the biomechanism of the anticancer drugs. 4. Clinical prospects Making sure the expression of MGMT and Topo-Ⅱ a and the in vitro chemosensitivity of common antiglioma drugs may give us important clues on the benefit of the rational choice of the approperiate personalized therapeutics of gliomas in clinical work. As a matter of fact, we can carry out a more rational, effective and personalized chemotherapy, based on the different expression of MGMT and Topo-Ⅱ a as well as the in vitro inhibition ratio of ACNU, TMZ and VM-26in the primary glioma culture in clinics. In this way, you can avoid abusing the invalid drugs, preventing the side-effects of these drugs and improve the long term outcomes of the glioma patients. |
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