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New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment
Article

Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells

by 1,2, 1,3,†, 1,4,†, 2, 2 and 1,5,*
1
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan
2
Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
3
Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
4
Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
5
Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(23), 5914; https://doi.org/10.3390/ijms20235914
Received: 17 October 2019 / Revised: 18 November 2019 / Accepted: 23 November 2019 / Published: 25 November 2019
(This article belongs to the Special Issue Cisplatin in Cancer Therapy: Molecular Mechanisms of Action)
Cisplatin is still the primary therapeutic choice for advanced lung cancers without driver mutations. The occurrence of cisplatin resistance is a major clinical problem in lung cancer treatment. The natural extracted agent emetine reportedly has anticancer effects. This study aimed to explore the possible role of emetine in cisplatin resistance. We used cell viability, Western blot, and Wnt reporter assays to show that emetine suppresses proliferation, β-catenin expression, and Wnt/β-catenin signaling in non-small cell lung cancer (NSCLC). The synergism of emetine and cisplatin was assessed by constructing isobolograms and calculating combination index (CI) values using the Chou-Talalay method. Emetine effectively synergized with cisplatin to suppress the proliferation of cancer cells. Furthermore, nuclear β-catenin and cancer stem cell-related markers were upregulated in the cisplatin-resistant subpopulation of CL1-0 cells. Emetine enhanced the anticancer efficacy of cisplatin and synergized with cisplatin in the cisplatin-resistant subpopulation of CL1-0 cells. Taken together, these data suggest that emetine could suppress the growth of NSCLC cells through the Wnt/β-catenin pathway and contribute to a synergistic effect in combination with cisplatin. View Full-Text
Keywords: emetine; cisplatin resistance; lung cancer; Wnt/β-catenin emetine; cisplatin resistance; lung cancer; Wnt/β-catenin
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MDPI and ACS Style

Wu, T.-H.; Chang, S.-Y.; Shih, Y.-L.; Huang, T.-W.; Chang, H.; Lin, Y.-W. Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells. Int. J. Mol. Sci. 2019, 20, 5914. https://doi.org/10.3390/ijms20235914

AMA Style

Wu T-H, Chang S-Y, Shih Y-L, Huang T-W, Chang H, Lin Y-W. Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells. International Journal of Molecular Sciences. 2019; 20(23):5914. https://doi.org/10.3390/ijms20235914

Chicago/Turabian Style

Wu, Ti-Hui, Shan-Yueh Chang, Yu-Lueng Shih, Tsai-Wang Huang, Hung Chang, and Ya-Wen Lin. 2019. "Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells" International Journal of Molecular Sciences 20, no. 23: 5914. https://doi.org/10.3390/ijms20235914

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