Experimental study on the therapeutic effects of nimustine combined with cisplatin on C6 brain glioma

Abstract

Objective:To observe the synergistic effects of nimustine(ACNU) and cisplatin(CDDP) in the treatment of glioma,and investigate the theoretical basis for the combined chemotherapy in clinic.Methods: The cell cycle and apoptosis of C6 glioma cells were examined by flow cytometry after treatment with ACNU plus CDDP for 24 h in vitro.C6 glioma cells were transplanted into the brain of Wistar rats to establish the C6 brain glioma model.The Wistar rats were treated with ACNU plus CDDP for 3 days,and then some rats were sacrificed.Morphological changes of tumor tissues were examined by HE staining.The protein expression of proliferating cell nuclear antigen(PCNA) and apoptosis-associated gene bcl-2 were tested by immunohistochemical method.The survival time of the Wistar rats were observed.Results: The FCM test found that there was no significant difference in cell cycle distribution between combined therapy group and single ACNU therapy group.The apoptotic rate increased after combined therapy [(2.10±0.14)%] compared with single CDDP therapy group [(1.72±0.21)%] and ACNU single therapy group [(0.57±0.01)%].The difference was significant(P0.01).Histological examination revealed the decreased number of the invaded focuses in the margin of the tumor body.Immunohistochemistry analysis indicated that the protein expression levels of PCNA and bcl-2 decreased compared with single therapy group(P0.01).The rats in the combined therapy group had longer survival time compared with those received single therapy.The difference was significant(P0.01).Conclusion: The combination of ACNU plus CDDP has apparent synergistic effects in the treatment of malignant brain glioma compared with single drug therapy.