title: Capecitabine metronomic chemotherapy inhibits the proliferation of gastric cancer cells through anti-angiogenesis.
abstract: To evaluate the inhibitory effect and mechanism of capecitabine metronomic chemotherapy on gastric cancer cells. In vitro, the effects of 5-fluorouracil (Fu) metronomic chemotherapy on proliferation, apoptosis, tube formation ability, and angiogenesis were detected. In vivo, Ki-67, CD34 and VEGF were detected by immunohistochemical staining (IHC). Flow cytometry was used to detect the percentage of circulating endothelial progenitors (CEPs), and VEGF and PDGF were detected by ELISA in the peripheral blood of nude mice. The proliferation of the SGC-7901 and AGS gastric cancer cell lines in the metronomic 5-Fu group was decreased compared with the control group in vitro. The total length of the small tubes and tubular junction numbers were significantly lower in the metronomic group than the control group. The VEGF and PDGF levels in the cell culture supernatants were lower in the metronomic group than the control group. Compared with the control group, the CEP percentage was decreased in the peripheral blood of tumor-bearing nude mice following treatment with metronomic 5-Fu or capecitabine chemotherapy. No significant changes were found in the conventional or control group. In the peripheral blood of tumor-bearing nude mice, the VEGF and PDGF levels were decreased in the metronomic groups. Metronomic 5-Fu inhibited the proliferation of gastric cancer cells in vitro and in vivo, and their antitumor effects were non-inferior to those of conventional dose chemotherapy, with mild side effects. Thus, tumor inhibition may be attributed to anti-angiogenesis.
authors: Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Fei
authors: F
authors: Yuan
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Hailong
authors: H
authors: Shi
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Jun
authors: J
authors: Ji
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Qu
authors: Q
authors: Cai
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Xuehua
authors: X
authors: Chen
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Yingyan
authors: Y
authors: Yu
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Bingya
authors: B
authors: Liu
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Zhenggang
authors: Z
authors: Zhu
authors: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors: Jun
authors: J
authors: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000098:blood supply / Q000473:pathology*; D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001772:Blood Cell Count; D000069287:Capecitabine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003470:Culture Media; D004354:Drug Screening Assays, Antitumor; D066026:Endothelial Progenitor Cells / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009024:Morphogenesis / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D012844:Sincalide / Q000032:analysis; D013274:Stomach Neoplasms / Q000097:blood / Q000098:blood supply / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D003470:Culture Media; D010982:Platelet-Derived Growth Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069287:Capecitabine; D012844:Sincalide; D005472:Fluorouracil