In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 1715-1715
Abstract:
Cytochrome P450 1B1 (CYP1B1) is a key enzyme involved in metabolizing environment pollutants and whose expression is often significantly increased in human malignancies. In the past years, several studies focused on the possible role of CYP1B1 in tumor progression, invasion and drug resistance. CYP1B1 gene polymorphisms have been associated with the risk of lung and other cancer. However, there is no a evidence that induction of CYP1B1 by B(a)P has relevance to anticancer drug resistance. In this study, we found that CYP1B1 expression was increased by exposure of B(a)P in A549 cells and H1299 cells, respectively. Both A549 cells and H1299 cells prolonged exposed to B(a)P [A549-B(a)P and H1299-B(a)P] were resistant to cisplatin treatments. MTT assay showed that IC50 of A549-B(a)P and H1299-B(a)P was 2.3 folds and 3.2 folds higher than IC50 of parental cells. Results of immuocytostain revealed that induction of CYP1B1 and AhR was detected in A549-B(a)P and H1299-B(a)P. Reduction of CYP1B1 by shRNA of CYP1B1 in A549-B(a)P and H1299-B(a)P became to be sensitized to cisplatin treatments. The similar result was found in A549 cells and H1299 cells transfected with shRNA of AhR. Our data suggested that AhR-mediated CYP1B1 expression affected the response of cisplatin treatments on non-small cell lung cancer cells (NSCLCs). It suggested that, in exposure of B(a)P on lung cancer cells, AhR can modulate CYP 1B1 expression resulting in producing BPDE to form a bulk of DNA adducts. Exposure of B(a)P is committed to controlling proliferative/apoptotic balance, which has obvious and important implications in tumor progression and drug resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1715. doi:10.1158/1538-7445.AM2011-1715
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-1715
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
