Chen Feihong, Wang Dan
Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast UniversityNanjing 211189, China.
Am J Transl Res. 2017 May 15;9(5):2243-2254. eCollection 2017.
Development of the novel targeted therapies for glioblastoma multiforme is very important. Brachytherapy has been proven to provide a good alternative to surgical removal of the prostate, breast and cervix with reduced risk of certain long-term side effects. Thus, I brachytherapy was used to effect on the growth and invasion of glioma cells and . The inhibitory effect of I seeds on C6 cells proliferation was determined by MTT assay. A rat intracranial glioma model was established and the I seeds were implanted into the glioma area. CD31 expression was determined by immunohistochemical method to evaluate the angiogenesis. The ΔΨm detection and cell invasion assays were performed to detect the mitochondrial-induced apoptosis and invasion signaling in tumor cells. I brachytherapy could significantly inhibit C6 rat glioma cells growth and reduce cell viability . The seeds implantation also inhibited tumor growth in the rat glioma model and improved survival rate. Analysis revealed that ROS production and the intrinsic mitochondrial pathway of apoptosis was activated by I brachytherapy. The HE staining results revealed that the rat glioma model treated with I seeds exhibited better defined tumor margins and fewer invasive cells to the lateral striatum compared with the untreated group. The comparison of expression of CD31 in treated or untreated groups was performed to show that the I brachytherapy has potential antiangiogenic activity. Meanwhile, I brachytherapy can inhibit the growth and invasion of glioma cells via decreasing the expression of MMP-2 and MMP-9.
开发针对多形性胶质母细胞瘤的新型靶向治疗方法非常重要。近距离放射治疗已被证明是前列腺、乳腺和子宫颈手术切除的良好替代方法，可降低某些长期副作用的风险。因此，采用碘近距离放射治疗来影响胶质瘤细胞的生长和侵袭。通过MTT法测定碘籽源对C6细胞增殖的抑制作用。建立大鼠颅内胶质瘤模型，并将碘籽源植入胶质瘤区域。采用免疫组化方法检测CD31表达以评估血管生成。进行ΔΨm检测和细胞侵袭试验以检测肿瘤细胞中线粒体诱导的凋亡和侵袭信号。碘近距离放射治疗可显著抑制C6大鼠胶质瘤细胞生长并降低细胞活力。籽源植入还可抑制大鼠胶质瘤模型中的肿瘤生长并提高生存率。分析表明，碘近距离放射治疗可激活活性氧生成和凋亡的内源性线粒体途径。苏木精-伊红染色结果显示，与未治疗组相比，接受碘籽源治疗的大鼠胶质瘤模型肿瘤边界更清晰，向外侧纹状体侵袭的细胞更少。通过比较治疗组和未治疗组CD31的表达，表明碘近距离放射治疗具有潜在的抗血管生成活性。同时，碘近距离放射治疗可通过降低MMP-2和MMP-9的表达来抑制胶质瘤细胞的生长和侵袭。
