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Dynamic Contrast Enhanced Magnetic Resonance Imaging of an Orthotopic Pancreatic Cancer Mouse Model
Published on: April 18, 2015
Anticancer effect of dihydroartemisinin (DHA) in a pancreatic tumor model evaluated by conventional methods and
Winn Aung1, Chizuru Sogawa, Takako Furukawa
1Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. winn@nirs.go.jp
Background:
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.
Results:
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.
Conclusion:
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.
Insights
Dihydroartemisinin (DHA) effectively inhibits pancreatic cancer cell and tumor growth by reducing proliferation and inducing apoptosis. Optical imaging demonstrated DHA
Area of Science:
- Oncology
- Pharmacology
- Biomedical Imaging
Background:
- Dihydroartemisinin (DHA) exhibits anticancer properties against various cancer cells and tumors.
- Understanding the molecular mechanisms of DHA's antineoplastic effects is crucial.
- Pancreatic cancer remains a significant therapeutic challenge.
Purpose of the Study:
- To evaluate the anticancer effects of DHA in pancreatic cancer.
- To elucidate the underlying molecular mechanisms of DHA action.
- To assess DHA efficacy in preclinical models using noninvasive optical imaging.
Main Methods:
- Utilized pancreatic cancer cell line (BxPc-3-RFP) and in vitro/in vivo optical imaging.
- Assessed cell proliferation, apoptosis, and angiogenesis markers (PCNA, Bax, Bcl-2, VEGF).
- Employed flow cytometry, Hoechst staining, Western blotting, and immunohistochemistry.
Main Results:
- DHA inhibited cell proliferation and viability dose-dependently, inducing apoptosis.
- Observed down-regulation of PCNA and Bcl-2, and up-regulation of Bax.
- VEGF was down-regulated under normoxic conditions; optical imaging showed linear correlation with tumor burden.
Conclusions:
- DHA inhibits pancreatic cancer growth by affecting proliferation and apoptosis.
- DHA's antiangiogenic effect is complex and context-dependent.
- Optical imaging facilitates real-time efficacy assessment, supporting DHA as a potential pancreatic cancer therapeutic.
