Silencing of Pkm2 Increases the Efficacy of Docetaxel in Human Lung Cancer Xenografts in Mice

Overview

Journal Cancer Sci

Specialty Oncology

Date 2010 May 29

PMID 20507318

Citations 69

Authors

Hua-Shan Shi

Dan Li

Jing Zhang

Yong-Sheng Wang

Li Yang

Hai-Long Zhang

Xian-huo Wang

Bo Mu

Wei Wang

Yu Ma

Fu-Chun Guo

Yu-quan Wei

Affiliations

Soon will be listed here.

Abstract

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.

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