Xia Zhi-bai, Wu Xin-jian, Qi Tie-wei, Huang Zheng-song
Department of Neurosurgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhongguo Zhong Yao Za Zhi. 2008 Sep;33(17):2150-3.
To explore the inhibitory effect of arsenic trioxide (A(s2)O3) on the growth of rat C6 glioma cells (C6 cells) as well as finding out the feasibility of using As2O3 as chemotherapy of gliomas.
C6 cells were treated by different dose of As2O3 (1, 2, 4, 6 and 8 micromol L(-1)). MTT assay and staining for PCNA were used for cell proliferation. Cell apoptosis was determined by TUNEL method and Bcl-2 expression was studied by Western blot. Parental rat C6 cells (5 x 10(5)/15 microL) were implanted into right caudate nucleus of male SD rats as control group. Rats bearing cerebral C6 gliomas as treated group were treated with 1 mmol x L(-1) As2O3. The general manifestation, survival time, MRI dynamic scanning and histopathological changes of all rats were observed.
All the treated cells showed decreased proliferation in vitro as detected by MTT method (P < 0.01) and staining for PCNA. In situ labeling apoptotic DNA fragment of the treated cells demonatrated that the cell apoptosis significantly increased following treatment with As2O3 (P < 0.01). Western blot showed that the expression of Bcl-2 protein was decreased. All rats in control group died of cerebral gliomas within 3 weeks after implantation of C6 cells (17.8 +/- 0.92) d. Eight out of 10 rats in treated group died within 24-36 days (32.1 +/- 1.35) d and other 2 ones kept alive beyond 120 days with one treated rat being totally disappear of the tumor foci and another having a little residue of tumor.
The result demonstrates the potential efficacy of As2O3 in the treatment of gliomas. It also suggests that As2O3 may be a good candidate for chemotherapy of human gliomas.
探讨三氧化二砷（As₂O₃）对大鼠C6胶质瘤细胞（C6细胞）生长的抑制作用，以及As₂O₃用于胶质瘤化疗的可行性。
用不同剂量的As₂O₃（1、2、4、6和8 μmol/L）处理C6细胞。采用MTT法和PCNA染色检测细胞增殖。通过TUNEL法测定细胞凋亡，并通过蛋白质印迹法研究Bcl-2表达。将亲代大鼠C6细胞（5×10⁵/15 μL）植入雄性SD大鼠的右侧尾状核作为对照组。将荷脑C6胶质瘤的大鼠作为治疗组，用1 mmol/L As₂O₃进行治疗。观察所有大鼠的一般表现、生存时间、MRI动态扫描和组织病理学变化。
MTT法和PCNA染色检测显示，所有处理组细胞的体外增殖均降低（P<0.01）。处理组细胞原位标记凋亡DNA片段表明，As₂O₃处理后细胞凋亡显著增加（P<0.01）。蛋白质印迹法显示Bcl-2蛋白表达降低。对照组所有大鼠在植入C6细胞后3周内死于脑胶质瘤（17.8±0.92）天。治疗组10只大鼠中有8只在24 - 36天内死亡（32.1±1.35）天，另外2只存活超过120天，其中1只治疗大鼠肿瘤病灶完全消失，另1只残留少量肿瘤。
结果表明As₂O₃在胶质瘤治疗中具有潜在疗效。这也提示As₂O₃可能是人类胶质瘤化疗的良好候选药物。
