The Overexpression of ABCG2 Reduces the Efficacy of Volasertib (BI 6727) and GSK641364 in Human S1-M1-80 Colon Carcinoma Cells


  • Sung-Han Hsiao Graduate Institute of Biomedical Sciences
  • Shi-Yu Luo Graduate Institute of Biomedical Sciences
  • Ching-Ya Su Graduate Institute of Biomedical Sciences
  • Wei-Cherng Tuo Graduate Institute of Biomedical Sciences
  • Cheng-Ting Chiang Graduate Institute of Biomedical Sciences
  • Yan-Qing Li Department of Physiology and Pharmacology
  • Yang-Hui Huang Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan
  • Chung-Pu Wu Graduate Institute of Biomedical Sciences : Department of Physiology and Pharmacology : Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan



ABCG2, multidrug resistance, Polo-like kinase 1, volasertib, GSK641364.


 The polo-like kinase 1 (Plk1) is one of the key regulators in cell cycle progression. Plk1 is overexpressed in many types of cancer and promotes the proliferation of cancer cells. Inhibition of Plk1 activity induces G2/M cell cycle arrest and reduces cancer cell viability. Volasertib and GSK461364 are selective inhibitors of Plk1, active against a wide range of tumor cells at nanomolar concentrations. In this study, while examining the effectiveness of Plk1 inhibitors against multiple human colon cancer cell lines, we discovered that the overexpression of ATP-binding cassette (ABC) drug transporter ABCG2 in human S1-M1-80 colon cancer cells confers resistance to volasertib and GSK461364. Moreover, we found that ABCG2-transfected HEK293 cells were also resistant to both Plk1 inhibitors. We revealed that volasertib and GSK461364 inhibited the function of ABCG2 in a concentration dependent manner, and had no significant effect on the protein expression of ABCG2. More importantly, we showed that the G2/M cell cycle arrest induced by volasertib or GSK461364 was significantly reduced in S1-M1-80 cells, and that ABCG2-mediated drug resistance to Plk1 inhibitors can be restored by inhibition of ABCG2 function. Therefore, the development of ABCG2-mediated drug resistance to volasertib and GSK461364 in cancer clearly present a significant therapeutic challenge, and a better treatment strategy should be further investigated.


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How to Cite

Sung-Han Hsiao, Shi-Yu Luo, Ching-Ya Su, Wei-Cherng Tuo, Cheng-Ting Chiang, Yan-Qing Li, Yang-Hui Huang, & Chung-Pu Wu. (2014). The Overexpression of ABCG2 Reduces the Efficacy of Volasertib (BI 6727) and GSK641364 in Human S1-M1-80 Colon Carcinoma Cells. Journal of Cancer Research Updates, 3(2),  108–116.




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