Department of Neurosurgery, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou, P.R. China.
Department of Neurosurgery, Forth Affiliated Hospital of Nantong University, Yancheng, P.R. China.
J Cell Biochem. 2018 Jul;119(7):6057-6064. doi: 10.1002/jcb.26803. Epub 2018 Mar 25.
Previous studies showed Demethoxycurcumin (DMC) has stronger anti-glioma and anti-GSCs effects both in vitro and in vivo. In addition, DMC seems to be lower toxicity than TMZ on nude mice. However, this conclusion was confirmed to be wrong in this study. We have evaluated the antitumor efficacy of DMC or TMZ treatment by an orthotopic glioblastoma xenograft model. Nude mice were injected with U87MG-luc cells in the caudate nucleus of the brain and treated with DMC (30 mg/kg q.d.) or TMZ (10 mg/kg q.d.) by intraperitoneal injection. Bioluminescence imaging (BLI) was used to monitoring tumor growth and response to therapy. Western blot was used to detect the expression of p-Akt, cleaved-caspase-3 and Bax. The average value of BLI showed TMZ determined a significant tumor regression while DMC had a mild regression effect on tumor growth compared with control group. Immunohistochemistry for Ki67, proliferating cell nuclear antigen (PCNA), and TUNEL demonstrated that TMZ more effectively inhibited the expression of Ki67 and PCNA, and increased the ratio of TUNEL-positive cells in in situ tumor tissue. Western blot analysis also indicated that TMZ but not DMC more significantly decreased p-Akt and increased cleaved-caspase-3 and Bax expression.These findings suggested a fact that TMZ appear to be more effective in controlling the growth of glioblastoma than DMC in an orthotopic glioblastoma xenograft model.
先前的研究表明，去甲氧基姜黄素（DMC）在体外和体内对神经胶质瘤和神经干细胞均具有更强的抗作用。此外，DMC 似乎比 TMZ 在裸鼠中的毒性更低。然而，本研究证实了这一结论是错误的。我们通过原位神经胶质瘤异种移植模型评估了 DMC 或 TMZ 治疗的抗肿瘤疗效。裸鼠在尾状核脑内注射 U87MG-luc 细胞，并通过腹腔注射给予 DMC（30mg/kg q.d.）或 TMZ（10mg/kg q.d.）。生物发光成像（BLI）用于监测肿瘤生长和对治疗的反应。Western blot 用于检测 p-Akt、cleaved-caspase-3 和 Bax 的表达。BLI 的平均值显示 TMZ 确定了肿瘤的显著消退，而 DMC 与对照组相比对肿瘤生长有轻微的消退作用。Ki67、增殖细胞核抗原（PCNA）和 TUNEL 的免疫组织化学染色表明，TMZ 更有效地抑制了 Ki67 和 PCNA 的表达，并增加了原位肿瘤组织中 TUNEL 阳性细胞的比例。Western blot 分析还表明，TMZ 而非 DMC 更显著地降低了 p-Akt 的表达，增加了 cleaved-caspase-3 和 Bax 的表达。这些发现表明，在原位神经胶质瘤异种移植模型中，TMZ 似乎比 DMC 更有效地控制神经胶质瘤的生长。
