Cancer Lett. 2012 Aug 28;321(2):128-36. Epub 2012 Jan 20.

Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancer.

Yoon YK, Im SA, Min A, Kim HP, Hur HS, Lee KH, Han SW, Song SH, Youn Oh D, Kim TY, Ho Kim W, Bang YJ.

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Cancer Research Institute, Seoul National University, Seoul 110-799, South Korea.

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.

PMID:: 22266184; [PubMed - in process]

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Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancer.

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