Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2524665 | Biomedicine & Pharmacotherapy | 2016 | 9 Pages |
Abstract
Sunitinib, a multi-targeted tyrosine kinase inhibitor, has been widely used in the therapy of advanced renal cell cancer and imatinib-resistant gastrointestinal stromal tumors. However, little benefits could be obtained from sunitinib for patients with other types of solid tumors including colorectal cancer (CRC). Ethaselen (BBSKE), a specific thioredoxin reductase 1 inhibitor, has shown convincing anticancer effects both in vivo and in vitro. In this study, we explored the combinatory effect of sunitinib and BBSKE in human CRC cell lines LoVo, HT-29 and RKO. Cotreatment of BBSKE and sunitinib with the ratio of 2:1 for 24Â h displayed synergistic effect against CRC cells proliferation. Apoptosis analysis also revealed that combination treatment of BBSKE and sunitinib (2:1) for 24Â h induced higher apoptosis rate than either single treatment. The synergistic effect against LoVo cells proliferation may be explained by sharp reduction of Bcl-2/Bax protein expression ratio, decrease of pro-Caspase-3 protein expression along with significantly augmented Caspase-3 enzymatic activity, and release of cytochrome C from mitochondria to cytoplasm in the combination treatment group. The significant inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation might also account for the synergism in cotreatment group. In short, sunitinib plus BBSKE is perhaps a promising strategy for colorectal cancer therapy.
Keywords
Dose-reduction indexVEGFRsBBSKEDRISRBVEGFRTKITrxTrxRBcl-2/BaxROSthioredoxin reductasethioredoxinSunitinibColorectal cancerNSCLCNon-small cell lung cancersulforhodamine Bcytochrome ccombination indexTyrosine kinase inhibitorCRCReactive oxygen speciesVascular endothelial growth factor receptorsplatelet-derived growth factor receptors
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Authors
Xiaoqing Zheng, Yunhan Zhang, Lei Zhang, Wei Xu, Weiwei Ma, Ruoxuan Sun, Huihui Zeng,