Demethoxycurcumin analogue DMC-BH exhibits potent anticancer effects on orthotopic glioblastomas.
Demethoxycurcumin analogue DMC-BH exhibits potent anticancer effects on orthotopic glioblastomas.
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去甲氧基姜黄素类似物 DMC-BH 对原位胶质母细胞瘤表现出有效的抗癌作用
DOI：
10.18632/aging.103981
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发表时间：
2020-11-18
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Shi L;Sun G;Zhang Y
去甲氧基姜黄素（DMC）在体外和皮下异种移植肿瘤中具有抗胶质瘤作用。我们前期的研究证实该分子在体内对原位胶质母细胞瘤也有轻微的抗胶质瘤作用。在这项研究中，我们发现DMC类似物DMC- bh比DMC表现出更强的体外和体内活性。DMC-BH对多种胶质瘤细胞包括SHG-44、C6、U251、U87、A172和原发性胶质瘤细胞均有细胞毒性。DMC-BH活性具有低急性毒性和适当的药代动力学特征。我们在异位异种移植模型、原位胶质母细胞瘤异种移植模型和患者源性肿瘤异种移植（PDTX）模型中评估了DMC-BH的抗肿瘤作用。DMC-BH在异位异种移植物和PDTX模型中均表现出强大的抗肿瘤活性。事实上，生物发光测量表明，DMC- bh对原位胶质瘤生长的抗肿瘤作用明显大于DMC。免疫组化分析显示，DMC-BH抑制Ki67的表达，增加tunel阳性细胞的发生率。Western blot结果显示，DMC-BH显著降低了原位胶质瘤组织中p-Akt和p-mTOR的表达。这些结果表明DMC类似物DMC- bh具有有效的抗肿瘤特性，值得进一步研究。
Demethoxycurcumin (DMC) has anti-glioma effects in vitro and in subcutaneous xenotransplanted tumors. Our previous study confirmed that the molecule also has mild anti-glioma effects on orthotopic glioblastomas in vivo. In this study, we found that DMC-BH, a DMC analogue, exhibited more potent in vitro and in vivo activities than did DMC. DMC-BH was cytotoxic against various glioma cells including SHG-44, C6, U251, U87, A172 and primary glioma cells. DMC-BH activity was characterized by low acute toxicity and an appropriate pharmacokinetic profile. We evaluated the anti-tumor effects of DMC-BH in an ectopic xenograft model, an orthotopic glioblastoma xenograft model and a patient-derived tumor xenograft (PDTX) model. DMC-BH exhibited potent anti-tumor activity in both the ectopic xenograft and PDTX models. Indeed, bioluminescence measurements showed that DMC-BH exerted a significantly greater anti-tumor effect on orthotopic glioma growth than DMC. Immunohistochemical analysis revealed that DMC-BH inhibited expression of Ki67 and increased the incidence of TUNEL-positive cells. Western blotting showed that DMC-BH significantly decreased p-Akt and p-mTOR expression in orthotopic glioma tissues. These results suggest that the DMC analogue DMC-BH has potent anti-tumor properties that warrant further study.
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影响因子：
5.8
作者：
Kim, Bomi;Seo, Bohyung;Youn, Yu Seok
通讯作者：
Youn, Yu Seok
DOI：
10.1016/j.ijrobp.2011.12.086
发表时间：
2012-11-01
影响因子：
7
作者：
Kim, Young Suk;Kim, Se Hoon;Suh, Chang-Ok
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DOI：
10.1155/2012/396573
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
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作者：
Huang TY;Hsu CW;Chang WC;Wang MY;Wu JF;Hsu YC
通讯作者：
Hsu YC
DOI：
10.1124/jpet.114.212910
发表时间：
2014-07-01
影响因子：
3.5
作者：
Jane, Esther P.;Premkumar, Daniel R.;Pollack, Ian F.
通讯作者：
Pollack, Ian F.
影响因子：
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作者：
Leng, Liang;Zhong, Xiaojun;Shi, Lei
通讯作者：
Shi, Lei