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Article

Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells

  • Authors:
    • Guan Wang
    • Shaohua Chen
    • Holly Edwards
    • Xinming Cui
    • Li Cui
    • Yubin Ge
  • View Affiliations / Copyright

    Affiliations: National Engineering Laboratory of AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, P.R. China, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA, Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China
  • Pages: 2789-2794
    |
    Published online on: October 3, 2014
       https://doi.org/10.3892/or.2014.3525
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Abstract

Pancreatic cancer is an aggressive disease with a poor prognosis. Therefore, new treatment is urgently required. GX15-070 is a pan-Bcl-2 inhibitor which has shown promising antitumor activity in different malignancies. We previously demonstrated that clinically achievable concentrations of GX15-070 caused growth arrest in pancreatic cancer cell lines. However, they only induced minimal levels of apoptosis. We hypothesized that GX15-070 induced autophagy in pancreatic cancer cells which blocked apoptosis. In this study, we investigated the effects of GX15-070 on autophagy and the antitumor activities of the combination of GX15-070 and chloroquine (CQ), an autophagy inhibitor, in six pancreatic cancer cell lines. We found that GX15-070 treatment indeed induced autophagy in 5 of the 6 pancreatic cancer cell lines, reflected by the conversion of LC3B-I to LC3B-II and detection of autophagosomes by transmission electron microscopy. Furthermore, we found additive to synergistic antitumor interactions in all six cell lines by MTT assays. CQ significantly enhanced GX15-070-induced apoptosis in the cell line models, possibly due to downregulation of Bcl-2, Bcl-xL and Mcl-1 in the cells by the two agents. These results provide compelling evidence for the further development of the combination of GX15-070 and CQ in pancreatic cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Wang G, Chen S, Edwards H, Cui X, Cui L and Ge Y: Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells. Oncol Rep 32: 2789-2794, 2014.
APA
Wang, G., Chen, S., Edwards, H., Cui, X., Cui, L., & Ge, Y. (2014). Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells. Oncology Reports, 32, 2789-2794. https://doi.org/10.3892/or.2014.3525
MLA
Wang, G., Chen, S., Edwards, H., Cui, X., Cui, L., Ge, Y."Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells". Oncology Reports 32.6 (2014): 2789-2794.
Chicago
Wang, G., Chen, S., Edwards, H., Cui, X., Cui, L., Ge, Y."Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells". Oncology Reports 32, no. 6 (2014): 2789-2794. https://doi.org/10.3892/or.2014.3525
Copy and paste a formatted citation
x
Spandidos Publications style
Wang G, Chen S, Edwards H, Cui X, Cui L and Ge Y: Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells. Oncol Rep 32: 2789-2794, 2014.
APA
Wang, G., Chen, S., Edwards, H., Cui, X., Cui, L., & Ge, Y. (2014). Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells. Oncology Reports, 32, 2789-2794. https://doi.org/10.3892/or.2014.3525
MLA
Wang, G., Chen, S., Edwards, H., Cui, X., Cui, L., Ge, Y."Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells". Oncology Reports 32.6 (2014): 2789-2794.
Chicago
Wang, G., Chen, S., Edwards, H., Cui, X., Cui, L., Ge, Y."Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells". Oncology Reports 32, no. 6 (2014): 2789-2794. https://doi.org/10.3892/or.2014.3525
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