In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2878-2878
Abstract:
Background: c-Met is a receptor tyrosine kinase (RTK) that has been shown to be a potential target of therapy in a variety of human cancers. We investigated if c-Met served as a potential therapeutic target in esophageal squamous cell cancer (ESCC). Methods: Cytotoxicity (MTT) assay, cell migration assay and cell cycle analysis by flow cytometry were conducted in KYSE 510 and 170 ESCC cell lines (kindly provided by Dr. Yutaka Shimada) in response to various concentrations of c-met inhibitors, SU11274 and PHA665752. Apoptosis of ESCC cell lines was detected by TUNEL assay. Cell cycle regulatory proteins, cyclin A and B1, tumor suppressors including Rb, p53 p21 and p27, and intrinsic apoptotic factors were determined by Western blot analysis. Mice inoculated with KYSE 170 ESCC cell line were used to test therapeutic response of c-met inhibitors in vivo. Results: SU11274 and PHA665752 significantly suppressed viability and migration of KYSE 170 and 510 ESCC cells with decreased expression of phosphorylated c-Met (p-c-Met). Expression of p21, p27, p53 and Rb was upregulated in ESCC cell lines treated with c-Met inhibitors while inducing G1/G2 cell cycle arrest and apoptosis. Tumor growth in vivo was significantly suppressed in response to treatment with c-Met inhibitors with decreased expression of p-c-Met within the mice tumors. Conclusion: c-Met inhibitors exerted significant anticancer effects in vitro and in vivo for ESCC cell lines, suggesting that c-Met may serve as a potential therapeutic target for ESCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2878. doi:1538-7445.AM2012-2878
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-2878
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
