Original ContributionPharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer
Section snippets
Cells and chemosensitivity assessment
Human pancreatic carcinoma cell lines BxPC-3, AsPC-1, and SU.86.86 were purchased from the American Type Culture Collection (Manassas, VA, USA). HPAF-II and Hs 766T cells were kindly donated by Dr. Raj Puri, FDA/CBER (Bethesda, MD, USA); MIA PaCa-2 by Dr. Joseph Cullen, University of Iowa (Iowa City, IA, USA); PANC-1 by Dr. Michael Brownstein, J. Craig Venter Institute (Rockville, MD, USA); and the murine line PAN-02 by Dr. Anthony Sandler, Children's Hospital Medical Center (Washington, DC,
In vitro dose–response relationships of gemcitabine and ascorbate either alone or in combination
Dose–response relationships for either gemcitabine or ascorbate cytotoxicity were established in seven human (BxPC-3, AsPC-1, PANC-1, MIA PaCa-2, SU.86.86, HPAF-II, Hs 766T) and one murine (PAN-02) pancreatic cancer cell line. Initial studies established a dose range when cells were exposed to serial dilutions of either gemcitabine or ascorbate and assessed for chemosensitivity after 72 h by MTT assay. Dose–response curves and IC50 values for each cell line are shown in Fig. 1 ordered (1A–1H)
Discussion
Our strategy herein was to apply standard pharmacologic principles to evaluate the chemotherapy pairing of gemcitabine and ascorbate. The findings showed that combining clinically achievable concentrations of pharmacologic ascorbate with gemcitabine increased chemosensitivity across the spectrum of malignant phenotypes represented in our panel of pancreatic cancer cells (Fig. 1, Fig. 2, Fig. 3, Fig. 4, Table 1, Table 2). Using a combination ratio design [24], [25], this study provides evidence
Acknowledgments
This research was supported by an American Cancer Society Institutional Research Pilot Grant (QK84541F) and in part by the Intramural Research Program of the NIDDK, NIH, and The Hilton Family Foundation.
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