title: Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancer.
abstract: We evaluated the effects of sunitinib monotherapy and in combination with cisplatin in human gastric cancer cell lines. Sunitinib showed antiproliferative effect in gastric cancer cells line with high PDGFRA expression. Knockdown of PDGFRA showed that sunitinib sensitivity was correlated with the basal expression of PDGFRA. Synergistic growth inhibitory activity in combination with cisplatin was identified. We further explored how sunitinib potentiated the activity of cisplatin. We found that sunitinib treatment resulted in the down-regulation of ERCC1 expression via the modulation of PDGFRA expression in gastric cancer cells. The effect was verified via SNU484 xenograft model. Our data support the rationale of clinical trial using sunitinib in combination of cisplatin in gastric cancer.
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul 110-799, South Korea.
authors.forename: Young-Kwang
authors.initials: YK
authors.lastname: Yoon
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Ahrum
authors.initials: A
authors.lastname: Min
authors.forename: Hwang-Phill
authors.initials: HP
authors.lastname: Kim
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Hur
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Song
authors.forename: Do
authors.initials: D
authors.lastname: Youn Oh
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D004357:Drug Synergism; D004720:Endonucleases / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077210:Sunitinib
chemical_list: D004268:DNA-Binding Proteins; D007211:Indoles; D011758:Pyrroles; D020796:Receptor, Platelet-Derived Growth Factor alpha; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D000077210:Sunitinib