唑来膦酸抗肿瘤作用的研究进展

刘俊彦; 王哲海

doi:10.3969/j.issn.1000-8179.2012.12.016

唑来膦酸抗肿瘤作用的研究进展

doi: 10.3969/j.issn.1000-8179.2012.12.016

刘俊彦,
王哲海^,

山东省肿瘤医院内三科（济南市250117）

详细信息

通讯作者:
王哲海 E-mail: wzhai8778@sina.com

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- PDF下载量: 5
- 被引次数: 0
出版历程
- 收稿日期: 2011-07-20
- 修回日期: 2012-12-28

Research Progress on Antitumor Effects of Zoledronic Acid

Junyan LIU,
Zhehai WANG^,

Department of Oncology, Shandong Tumor Hospital, Ji'nan 250117, China

More Information

Corresponding author: Zhehai WANG;E-mail: wzhai8778@sina.com

摘要

摘要: 唑来膦酸作为第三代双膦酸盐药物已广泛用于恶性实体瘤骨转移相关事件的防治。进一步研究发现，唑来膦酸可通过抑制甲羟戊酸途径中焦磷酸合酶的活性，使异戊烯焦磷酸大量蓄积，同时异戊烯焦磷酸与细胞内一磷酸腺苷结合形成三磷酸腺苷分解类似物蓄积于细胞中，从而改变细胞周期蛋白和凋亡蛋白水平，抑制肿瘤细胞生长并促进其凋亡，具有一定的直接和/ 或间接抗肿瘤作用。有关肺癌、乳腺癌、前列腺癌及肝癌等前期临床试验提示唑来膦酸与细胞毒药物、内分泌药物及靶向药物联合具有一定程度的协同抗肿瘤作用，并且在抗肿瘤药物之后序贯应用效果更好。一些相关的临床试验正在进行中。
- 唑来膦酸 /
- 抗肿瘤 /
- 联合治疗 /
- 异戊烯焦磷酸 /
- 骨转移
Abstract: Zoledronic acid (ZOL), a third-generation bisphosphonate, has been widely used for the treatment of skeletal-related events in malignant solid tumors. Previous studies have demonstrated that ZOL can induce direct and indirect antitumor activities through pyrophosphate synthase inhibition, which blocks the mevalonate pathway and causes isopentenyl pyrophosphate (IPP) accumulation. IPP becomes conjugated to AMP to form a novel ATP analog. The amount of IPP and ATP analog is correlated with cyclin and apoptotic protein levels, which are associated with cell line growth and apoptosis. Preclinical studies on lung cancer, breast cancer, prostate cancer, liver cancer, and so on, confirmed a synergistic effect between ZOL and cytotoxic, endocrine, and targeted drugs. The observed improvement in antitumor effects by using combination therapy with ZOL is currently being verified through additional clinical trials.
- Zoledronic acid (ZOL) /
- Antitumor /
- Combination therapy /
- Isopentenyl pyrophosphate (IPP) /
- Skeletal-related events

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参考文献(16)

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