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The role of the SHH gene in prostate cancer cell resistance to paclitaxel
Author(s) -
Statkiewicz Malgorzata,
Maryan Natalia,
Lipiec Agnieszka,
Grecka Emilia,
Grygorowicz Monika A.,
Omiotek Marcin,
Gorska Agnieszka,
Mikula Michal,
Malecki Maciej
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22830
Subject(s) - du145 , lncap , sonic hedgehog , cancer research , paclitaxel , biology , cancer cell , prostate cancer , cancer , microbiology and biotechnology , signal transduction , genetics
BACKGROUND The increased activity of the Sonic Hedgehog (SHH) pathway has been demonstrated in many types of cancer including prostate cancer (PCa). It has been shown that SHH pathway is involved in tumor angiogenesis and in regulation of metabolism of cancer stem cells. The increased activity of the SHH pathway is responsible for generation and maintenance of the multidrug resistance in cancer cells. A key role in the development of this insensitivity to cytotoxic drugs play ATP‐binding cassette (ABC) transporters. METHODS SHH encoding plasmid was stably transfected into PCa cell lines DU145 and LNCaP. The expression of SHH was silenced by shRNA and the level of SHH was tested by quantitative (q)PCR and western blot methods. The effect of SHH overexpression in cells after treatment with paclitaxel was measured by MTT assay, crystal violet assay and flow cytometry. The level of 44 ABC transporters was estimated by qPCR. RESULTS Expression of exogenous SHH protein in DU145 and LNCaP cell lines enhanced their resistance to paclitaxel along with increased expression of ABC transporters transcripts. Paclitaxel treatment further enhanced the expression of increased ABC transporters transcripts in cells overexpressing SHH. CONCLUSIONS Overexpression of SHH enhances PCa cell lines resistance to paclitaxel. Higher level of SHH leads to increase in ABC transporters expression in a manner dependent on paclitaxel. Prostate 74:1142–1152, 2014 . © 2014 Wiley Periodicals, Inc.