Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer

Chun Wun Lu, Shau Chieh Lin, Chun Wei Chien, Shih Chieh Lin, Chung Ta Lee, Bo Wen Lin, Jenq Chang Lee, Shaw Jenq Tsai

研究成果: Article同行評審

95 引文 斯高帕斯(Scopus)


The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and is associated with tumor malignancy. Pyruvate dehydrogenase kinase-1 (PDK1) and PDK3 participate in the metabolic switch of cancer cells; however, the medical significance of PDK1 and PDK3 in cancer progression is not known. Here, we assessed the expression profiles of PDK1 and PDK3 in colorectal cancer. Western blot analysis (n = 74) demonstrated that PDK3 was markedly increased in colon cancer compared to that in adjacent normal tissues, whereas PDK1 was decreased in cancer cells. In addition, PDK3 expression was positively correlated with that of hypoxia inducible factor-1α (HIF-1α) in cancer cells. Further analysis using immunohistochemical staining revealed that PDK3 levels were positively associated with severity of cancer and negatively associated with disease-free survival. In vitro studies using several colon cancer cell lines showed that PDK3 expression was controlled by HIF-1α and contributed to hypoxia-induced increased drug resistance, perhaps explaining why patients with PDK3 overexpression have a greater incidence of treatment failure. Taken together, our findings suggest that PDK3 plays an important role in the metabolic switch and drug resistance of colon cancer and is potentially a novel target for cancer therapy.

頁(從 - 到)1405-1414
期刊American Journal of Pathology
出版狀態Published - 2011 9月

All Science Journal Classification (ASJC) codes

  • 病理學與法醫學


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