C-myb和蛋白激酶C_α在脑胶质瘤侵袭性生长时相互作用的实验研究

Experimental Study of Association between C-myb and PKC_α Expression during Cerebral Glioma Invasion

背景和目的:侵袭性生长是脑胶质瘤的生物学特征之一,也是导致治疗困难的重要原因之一。本文旨在研究脑胶质瘤在体内侵袭性生长过程中,C-myb核内癌基因与蛋白激酶C_α之间的相互作用。方法:Wistar大鼠30只,于右侧大脑皮层运动区种植C_6胶质瘤细胞(3×10~6)。术后第10天将大鼠全部处死取材,进行大体观察、HE染色及免疫组织化学检查,并对C-myb、蛋白激酶C_α免疫组织化学阳性表达进行评分。利用SPSS统计软件评价肿瘤区、肿瘤边缘区的C-myb与蛋白激酶C_α表达评分的相关关系。结果:30只大鼠脑内种植C_6胶质瘤细胞10天后,均可见肿瘤生长,其中28只大鼠大体观察及HE染色见肿瘤向其周围呈侵袭性生长;肿瘤区、肿瘤边缘区的C-myb、蛋白激酶C_α均可见阳性表达,两者的阳性表达评分密切相关(P<0.05);正常脑组织中,C-myb及蛋白激酶C_α均为阴性表达。结论:C-myb可能是决定胶质瘤侵袭性的重要癌基因。其直接作用是促进胶质瘤细胞的增殖,间接作用可能是通过提高胞浆内Ca^(2+)浓度,激活PKC_α,使肿瘤细胞不断向周围脑组织侵袭。

BACKGROUND & OBJECTIVE: Invasive growth is one of the most important biological charac-teristics of glioma. The invasiveness makes treatment difficult. In this study, the correlation between C-myb and PKCα expression during invasive growth of cerebral glioma was investigated using rat glioma models. METH-ODS: Thirty male Wistar rats were implanted with 3×10~6 C6 glioma cells in the right cerebral cortex to produce glioma models. All rats were sacrificed after 10 days and examined histologically using HE staining and immunohisto-chemistry (IHC).The positive expression of C-myb and protein kinase Cα (PKCα) was determined with IHC meth-ods in the samples of the center of the tumor, the margin surrounding the tumor and normal brain tissues. The correlation of the expressing scores between the C-myb and PKCα was analyzed. RESULTS: Ten days after the C6 glioma cell implantation, tumor masses formed in all the rats. In 28 rats, glioma cells were found invading into the surrounding brain tissues. In the center of the tumor and the margin surrounding the tumor, C-myb and PKCα were positively expressed. The expression score of C-myb correlated significantly (p<0. 05) with that of PKCα in both the center of tumor and the margin surround-ing the tumor. While the C-myb and PKCα expres-sion was negative in the normal brain tissues.CONCLUSION: Our data suggest that C-myb may be an important oncogene during glioma inva- sive growth. The direct effect of C-myb could promote tumor cell proliferation. The indirect effect of C-myb could raise the Ca^(2+) concentration in the cytoplasma, which then activates the PKCα. The direct and indirect effects result in glioma cell invasion.