In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 902-902
Abstract:
Lung cancer is the leading cause of cancer deaths worldwide with non-small cell lung cancer (NSCLC) accounting for ∼85% of diagnosed cases. The 5 year survival rate for NSCLC is ∼15% with less than 7% of the patients alive 10 years after initial diagnosis. The taxanes, docetaxel and paclitaxel are potent chemotherapeutic drugs which result in cell cycle arrest and apoptosis through inhibition of microtubule depolymerization and are fundamental in cancer treatment regimens and are used as first line agents in NSCLC. Chemoresistance is a major obstacle in the treatment of NSCLC, an observation attributed in part to the drug efflux activity of the ATP Binding Cassette (ABC) transporter family proteins. ABCC10, a member of the ABC transporter family has been shown to confer resistance to various anti-neoplastic agents including docetaxel and paclitaxel in vitro. More importantly, Abcc10 null mice have been shown to exhibit increased tissue sensitivity to paclitaxel in vivo. Thus, ABCC10 may be an ideal target for investigation as a factor involved in reducing taxane efficacy. Here, we investigate whether ABCC10 has a role in taxane resistance in non-small cell lung carcinoma. Human NSCLC cell lines were examined for ABCC10 expression by western immunoblots ABCC10 expression was then targeted for suppression using short-hairpin RNAs in the NSCLC cell lines A549 and H1299. Our results show that ABCC10 is expressed at varying levels in human NSCLC cell lines. Furthermore, suppression of ABCC10 in NSCLC cell lines resulted in increased cellular accumulation of docetaxel as well as a reduction in the efflux of the drug out of the cells. Further studies are needed to assess effects of ABCC10 in vivo on docetaxel sensitivity as well as the mechanisms involved in regulating ABCC10 activity. Citation Format: Janet Wangari-Talbot, Bruce Zhang, Elizabeth Hopper-Borge. Role of ABCC10 in taxane mediated resistance in non-small cell lung carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 902. doi:10.1158/1538-7445.AM2013-902
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-902
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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