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Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, Zhejiang, China
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Int. J. Mol. Sci. 2019, 20(21), 5250; https://doi.org/10.3390/ijms20215250
Received: 16 September 2019 / Revised: 18 October 2019 / Accepted: 21 October 2019 / Published: 23 October 2019
(This article belongs to the Special Issue Drug Transporters)
A deep insight into the function and kinetics of ATP-binding cassette (ABC) transporters may aid in the development of pharmaceutics that can minimize the particular facet of chemo-resistance. We utilized bioluminescence imaging to monitor the ABC transporter mediated intracellular drug efflux function. We also investigated the potential association between the intracellular bioluminescent pharmacokinetic profiles and the anti-tumor efficacy of the coix seed extract and gemcitabine against pancreatic cancer cells in vitro and in vivo. The bioluminescent pharmacokinetic parameters and pharmacodynamic index (IC50 and TGI) were determined. The expression levels ABCB1 and ABCG2 were assessed. Results showed that coix seed extract could synergistically enhance the anti-cancer efficacy of gemcitabine (p < 0.05). Meanwhile coix seed extract alone or in combination with gemcitabine could significantly increase the AUCluc while decreasing the Kluc (p < 0.01). Western blot and immunohistochemistry assay demonstrated that coix seed extract could significantly mitigate gemcitabine-induced upregulation of ABCB1 and ABCG2 protein. The Pearson correlation analysis demonstrated that the bioluminescent pharmacokinetic parameters and pharmacodynamic index have strong association in vitro and in vivo. In conclusion coix seed extract could augment the efficacy of gemcitabine therapy in pancreatic cancer cells may at least partly due to the alteration of ABC transporter-mediated drug efflux function. View Full-Text
Keywords: coix seed extract; ATP-binding cassette (ABC) transporters; gemcitabine; bioluminescent pharmacokinetic profile; D-luciferin potassium salt; pancreatic cancer coix seed extract; ATP-binding cassette (ABC) transporters; gemcitabine; bioluminescent pharmacokinetic profile; D-luciferin potassium salt; pancreatic cancer
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MDPI and ACS Style

Qian, Y.; Xiong, Y.; Feng, D.; Wu, Y.; Zhang, X.; Chen, L.; Gu, M. Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study. Int. J. Mol. Sci. 2019, 20, 5250. https://doi.org/10.3390/ijms20215250

AMA Style

Qian Y, Xiong Y, Feng D, Wu Y, Zhang X, Chen L, Gu M. Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study. International Journal of Molecular Sciences. 2019; 20(21):5250. https://doi.org/10.3390/ijms20215250

Chicago/Turabian Style

Qian, Yifan, Yang Xiong, Di Feng, Yali Wu, Xu Zhang, Liping Chen, and Mancang Gu. 2019. "Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study" International Journal of Molecular Sciences 20, no. 21: 5250. https://doi.org/10.3390/ijms20215250

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