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J Cell Sci 114:1643–1653įrank CD, Boffa DJ, Tanoue LT (2009) The new lung cancer staging system. doi: 10.1097/01.pas.0000202048.28203.25ĭastoor Z, Dreyer JL (2001) Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. doi: 10.1038/nature06734Ĭolman H, Giannini C, Huang L, Gonzalez J, Hess K, Bruner J, Fuller G, Langford L, Pelloski C, Aaron J, Burger P, Aldape K (2006) Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.
#WAHL MODEL 9966 MOD#
Mod Pathol 13:17AĬhristofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. doi: 10.1158/0008-5472.CAN-06-2870īaehner R, Weidner N (2000) Enhanced mitotic figure counting in breast carcinomas using a mitosis-specific antibody: anti-phosphohistone-H3 (PHH3). doi: 10.1016/j.ygeno.2004.08.010Īttila S, Veress R, Ovádi J, Csermely P, Kéri G, Ullrich A (2007) Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. doi: 10.3322/CA.2007.0010Īltenberg B, Greulich KO (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. The enhanced antitumor activity of the combined treatment compared to treatment with shRNA alone may result in part from increased induction of apoptosis and augmented inhibition of cancer cell proliferation.Īhmedin J, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. Use of RNA interfering (RNAi) targeting PKM2 significantly inhibited tumor growth when combined with cisplatin in a human A549 lung cancer xenograft model. The cell proliferation rate, as determined by counting cells labeled with an anti-phospho-histone H3, a marker for mitosis, was lower in samples from animals treated with both cisplatin and shRNA than in samples from other groups ( P < 0.05). The levels of apoptotic cells were significantly higher in samples from animals in the combined treatment group than those from untreated animals ( P < 0.05). In the lung cancer xenograft model, average tumor volume in the group treated with both cisplatin and shRNA was statistically lower than those of other groups ( P < 0.05). ResultsĮxpression of shRNA targeting PKM2 resulted in inhibition of PKM2 expression in A549 cells. Apoptosis and cell proliferation status were examined to determine the mechanisms of tumor growth inhibition. In a human A549 lung cancer xenograft model, the effects of treatment with shRNA, with or without cisplatin, on tumor volume were determined. PKM2 expression levels were evaluated by Western blot analysis. The expression of PKM2 in A549 cells was determined by immunofluorescence. In this study, the effects of combined treatment with cisplatin (DDP) and a plasmid that expresses a short hairpin RNA (shRNA) targeting PKM2 on the growth of human A549 xenograft lung cancer model were investigated. Pyruvate kinase isoenzyme M2 (PKM2) is a key enzyme in aerobic glycolysis inhibition of PKM2 leads to the tumor growth inhibition.
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