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

Authors :: Yoon YK
Im SA
Min A
Kim HP
Hur HS
Lee KH
Han SW
Song SH
Youn Oh D
Kim TY
Kim WH
Bang YJ
Source :: Cancer letters [Cancer Lett] 2012 Aug 28; Vol. 321 (2), pp. 128-36. Date of Electronic Publication: 2012 Jan 20.
Publication Year :: 2012
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.<br /> (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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