Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
- PMID: 20507318
- PMCID: PMC11158281
- DOI: 10.1111/j.1349-7006.2010.01562.x
Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
Erratum in
- Cancer Sci. 2010 Jun;101(6):1575
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.
Figures






References
-
- Warburg OH. The Metabolism of Tumours. London: Constable and Co Ltd, 1930.
-
- Warburg O. On the origin of cancer cells. Science 1956; 123: 309–14. - PubMed
-
- Yeluri S, Madhok B, Prasad KR, Quirke P, Jayne DG. Cancer’s craving for sugar: an opportunity for clinical exploitation. J Cancer Res Clin Oncol 2009; 135: 867–77. - PubMed
-
- Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med 2008; 49(Suppl 2): 24S–42S. - PubMed
-
- Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev 2004; 4: 891–9. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous