Anticancer Effect of Dihydroartemisinin (DHA) in a Pancreatic Tumor Model Evaluated by Conventional Methods and Optical Imaging.
Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan. firstname.lastname@example.org.
Dihydroartemisinin (DHA) inhibits the growth of certain cancer cells and xenograft tumors. Further understanding of the molecular mechanisms and genetic participants that govern the antineoplastic effects of DHA is necessary. The anticancer effects of DHA and its underlying mechanisms in pancreatic cancer and the efficacy in animal models by noninvasive optical imaging were evaluated.
MATERIALS AND METHODS:
Combined with cell/tumor growth assays, flow cytometric analysis, and Hoechst staining, the effect of DHA was investigated using the pancreatic cancer cell line BxPc3-RFP stably expressing red fluorescence protein and in vitro/in vivo optical imaging. Proteins that regulate proliferation (PCNA), apoptosis (Bax and Bcl-2), and angiogenesis (vascular endothelial growth factor (VEGF)) were evaluated in cell and tumor samples by Western blotting and immunohistochemical analyses.
DHA inhibited the proliferation and viability of cells in a dose-dependent manner and induced apoptosis. We observed down-regulation of PCNA and Bcl-2, and up-regulation of Bax. VEGF was down-regulated by DHA in cells under normoxic, but not hypoxic, conditions. Fluorescence intensity emitted from cells and tumors correlated linearly with cell count and tumor burden, respectively.
DHA inhibits cell and tumor growth by interfering with cell proliferation and inducing apoptosis. The antiangiogenic effect of DHA appears to be a complicated process. Optical imaging supports the real-time assessment of DHA efficacy in a preclinical model and comprehensive analysis substantiates that DHA is a potential candidate for pancreatic cancer therapy.