Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
复制标题
沉默pkm2可提高多西紫杉醇对小鼠人肺癌异种移植物的疗效
DOI：
10.1111/j.1349-7006.2010.01562.x
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发表时间：
2010-06-01
期刊：
影响因子：
5.7
通讯作者：
Wei, Yu-quan
中科院分区：
文献类型：
--
作者：
Shi, Hua-shan;Li, Dan;Wei, Yu-quan
肿瘤有氧糖酵解，或称瓦伯格效应，在肿瘤存活、生长和转移中发挥着重要作用。丙酮酸激酶同工酶 M2 (PKM2) 是调节肿瘤细胞有氧糖酵解的关键酶。最近的研究表明，PKM2 可用作诊断的肿瘤标志物，特别是作为癌症治疗的潜在靶点。我们在体内和体外研究了靶向 PKM2 的 shRNA 和多西紫杉醇组合对人 A549 肺癌细胞的影响。我们观察到shRNA可以显着下调PKM2的表达水平。 PKM2的减少导致ATP合成减少，从而导致多西紫杉醇在细胞内蓄积。此外，pshRNA-pkm2 和多西紫杉醇的组合在体内和体外均抑制肿瘤生长并促进更多癌细胞凋亡。我们的研究结果表明，靶向肿瘤糖酵解可以提高化疗的疗效。特别是，在某种程度上，靶向 PKM2 可能成为逆转癌症治疗化疗耐药的一种新方法。 （癌症科学 2010）
Tumor aerobic glycolysis, or the Warburg effect, plays important roles in tumor survival, growth, and metastasis. Pyruvate kinase isoenzyme M2 (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent research has shown that PKM2 can be used as a tumor marker for diagnosis and, in particular, as a potential target for cancer therapy. We investigated the effects of combining shRNA targeting PKM2 and docetaxel on human A549 lung carcinoma cells both in vivo and in vitro. We observed that the shRNA can significantly downregulate the expression level of PKM2. The decrease of PKM2 resulted in a decrease in ATP synthesis, which caused intracellular accumulation of docetaxel. Furthermore, the combination of pshRNA‐pkm2 and docetaxel inhibited tumor growth and promoted more cancer cell apoptosis both in vivo and in vitro. Our findings suggest that targeting tumor glycolysis can increase the efficacy of chemotherapy. In particular, the targeting of PKM2 could, to some extent, be a new way of reversing chemotherapy resistance to cancer therapy. (Cancer Sci 2010)