Open AccessSilencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice
Author(s) -
Shi Huashan,
Li Dan,
Zhang Jing,
Wang Yongsheng,
Yang Li,
Zhang Hailong,
Wang Xianhuo,
Mu Bo,
Wang Wei,
Ma Yu,
Guo Fuchun,
Wei Yuquan
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01562.x
Subject(s) - pkm2 , docetaxel , cancer research , anaerobic glycolysis , warburg effect , in vivo , lung cancer , gene silencing , small hairpin rna , cancer cell , medicine , pyruvate kinase , pharmacology , cancer , apoptosis , biology , glycolysis , oncology , biochemistry , metabolism , microbiology and biotechnology , gene knockdown , gene
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)