title: Increase in E-selectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine.
abstract: E-selectin is expressed on the surfaces of stimulated vascular endothelial cells and is sometimes involved in cancer cell metastasis. The H2-receptor antagonist cimetidine inhibits the increase in E-selectin expression on vascular endothelial cells that is induced by interleukin-1beta (IL-1beta) and cimetidine. It also inhibits the adhesion of sialyl-Lewis-antigen-positive cancer cells to vascular endothelial cells, ultimately inhibiting hematogenous metastasis. Anticancer drugs are essential to cancer therapy, but whether they can alter the expression of E-selectin in vascular endothelial cells remains unclear. Whether cimetidine inhibits the expression of E-selectin in the same manner in the presence or absence of anticancer drugs also remains unknown. Human umbilical vein endothelial cells were cultured with 5-fluorouracil (5-FU), doxorubicin (DXR), cisplatin (CDDP), or IL-1beta and with or without cimetidine. The expression of E-selectin at the mRNA and protein levels was then determined using quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining, respectively. The E-selectin mRNA level increased in cells exposed to 5-FU, DXR, or CDDP, but the addition of cimetidine had no effect on the E-selectin mRNA level. The expression of E-selectin protein was also significantly higher after the addition of 5-FU, DXR, or CDDP, compared with that of a negative control. However, when cimetidine was added prior to the addition of 5-FU, DXR, or CDDP, the expression of E-selectin was significantly suppressed. Thus, cimetidine significantly inhibited the expression of E-selectin at the protein level without affecting its expression at the mRNA level in cells treated with anticancer drugs. In conclusion, anticancer drugs increased the expression of E-selectin and this increase was inhibited by cimetidine. These findings suggest that the administration of cimetidine during treatment with anticancer drugs might be useful for preventing metastasis.
authors.affiliation: Department of General and Gastrointestinal Surgery, School of Medicine, Fujita Health University, Aichi, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Kawase
authors.forename: Soji
authors.initials: S
authors.lastname: Ozawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Imaeda
authors.forename: Shunji
authors.initials: S
authors.lastname: Umemoto
authors.forename: Sumio
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D014471:Umbilical Veins / Q000378:metabolism*
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D019040:E-Selectin; D004791:Enzyme Inhibitors; D002927:Cimetidine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil