Anti-angiogenic effects of resveratrol in combination with 5-fluorouracil on B16 murine melanoma cells.
5-Fluorouracil (5-FU) has been used as a chemotherapeutic drug for various types of cancer, although the development of resistance remains a major limitation for its use in clinical settings. In the present study, the anti-angiogenic effects of resveratrol and 5-FU either alone or in combination were examined in a B16 murine melanoma model. Co-treatment using resveratrol and 5-FU inhibited cell proliferation more efficiently compared with use of either drug alone and the antiproliferative effect coincided with changes in the expression levels of AMP-activated protein kinase (AMPK), cyclooxygenase-2, vasodilator-stimulated phosphoprotein (VASP) and vascular endothelial growth factor (VEGF). Furthermore, co-treatment with resveratrol and 5-FU reduced tumor growth compared with that in the control group and this growth-inhibitory effect was associated with changes in the expression levels of AMPK, VASP and VEGF. Immunohistochemical staining for angiogenesis demonstrated that co-treatment with resveratrol and 5-FU reduced the number of microvascular vessels compared with that in the control group. These results suggested that co-treatment with resveratrol and 5-FU suppressed cell growth and angiogenesis in B16 murine melanoma tumors.
Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yusung‑gu, Daejeon 305‑811, Republic of Korea.
Sol Hwa
SH
Lee
Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yusung‑gu, Daejeon 305‑811, Republic of Korea.
Bong Seong
BS
Koo
Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yusung‑gu, Daejeon 305‑811, Republic of Korea.
Song Yi
SY
Park
Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yusung‑gu, Daejeon 305‑811, Republic of Korea.
Young Min
YM
Kim
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D000098662:Vasodilator-Stimulated Phosphoprotein; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol; D005472:Fluorouracil