In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3515-3515
Abstract:
Most non-small cell lung cancer (NSCLC) tumors with EGFR mutations are responsive to EGFR tyrosine kinase inhibitors such as gefitinib. Preliminary experiments with PC-9/MET, a gefitinib resistant cell line derived from PC-9 showed a higher sensitivity to SN-38, which is an active metabolite of CPT-11, in comparison to parental PC-9. The mechanisms of the collateral sensitivity to SN-38 were investigated in the resistant cell line. The WST-1 assay showed that PC-9/MET was more sensitive, with an IC50 of 0.027 ± 0.014 μM, to SN-38 than that to PC-9 with an IC50 of 0.093 ± 0.049 μM. Topoisomerase-I (Topo-I) mRNA expression value in PC-9/MET to increase 9.2 times in comparison to that of PC-9. The Topo-I activity of PC-9/MET was higher than that of PC-9 and the Topo-I protein expression was also higher in PC-9/MET. PC-9/MET has a greater expression of MET in comparison to PC-9. The suppression of MET expression by an MET-specific siRNA resulted in a decrease in the Topo-I activity and Topo-I protein expression in PC-9/MET. In conclusion, the Topo-I activity and protein expression in PC-9/MET is elevated via the mRNA expression, thus resulting in collateral sensitivity to SN-38. The MET over-expression in PC-9/MET may therefore be one of the mechanisms which cause an increase in the Topo-I activity and expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3515.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-3515
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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