Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer

Tai Kuang Chao, Tien Shuo Huang, Yu Ping Liao, Rui Lan Huang, Po Hsuan Su, Hueng Yuan Shen, Hung Cheng Lai, Yu Chi Wang

研究成果: 雜誌貢獻文章同行評審

33 引文 斯高帕斯(Scopus)

摘要

Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0.001), had poor progression-free survival rates (p = 0.01) as compared with patients exhibiting lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence interval: 0.70–5.85). In cell lines, PKM2 inhibitor significantly inhibited the glycolytic rate according to cellular glucose consumption (p < 0.001). We also utilized Seahorse assays to assess metabolism-related cell-specific factors and the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed attenuation of the extracellular acidification rate (p < 0.05) and no significant difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2 inhibitor suppressed ovarian cancer growth and cell migration in vitro and inhibited tumor growth without significant toxicity in a xenograft study. PKM2 inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth. Targeting PKM2 may constitute a promising therapy for patients with ovarian cancer, and clinical trials involving shikonin are warranted.
原文英語
文章編號e0182166
期刊PLoS One
12
發行號7
DOIs
出版狀態已發佈 - 7月 1 2017

ASJC Scopus subject areas

  • 醫藥 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 農業與生物科學 (全部)

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