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Antisense Bcl‐2 sensitizes prostate cancer cells to radiation
Author(s) -
Mu Zhaomei,
Hachem Paul,
Pollack Alan
Publication year - 2005
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.20303
Subject(s) - lncap , clonogenic assay , transfection , apoptosis , cell culture , prostate cancer , cancer research , biology , cancer cell , microbiology and biotechnology , medicine , cancer , biochemistry , genetics
BACKGROUND Bcl‐2 is anti‐apoptotic and overexpression is associated with prostate tumor aggressiveness. We hypothesized that Bcl‐2 has a role in prostate cancer radiation (RT) response. The relationship of Bcl‐2 expression in four prostate cancer cell lines, and the effect of modulating expression with a Bcl‐2 antisense oligonucleotide (G3139, Genasense®, oblimersen sodium, Genta Incorporated), to RT was examined. METHODS The four cell lines studied were LNCaP (wild type‐p53), PC3 (p53 null), Bcl‐2 stably transfected LNCaP (LNCaP‐BST), and Bcl‐2 stably transfected PC3 (PC3‐BST) cells. Cells were treated with antisense (AS) Bcl‐2 alone or with RT (2‐6 Gy). Following RT, cells were processed at 3–6 hr for Western blots, 18 hr for Annexin V staining and flow cytometric analysis, 24 hr for caspases 3 + 7 quantification by fluorometric assay, and immediately for clonogenic survival. RESULTS AS caused a significant reduction in Bcl‐2 expression in all cell lines. P53 expression was elevated following RT treatment in LNCaP and LNCaP‐BST cells. P21 was increased by RT treatment in all cell lines. AS caused a significant increase in caspase 3 + 7 activity over the mismatch (MM) controls in all cell lines. When AS was combined with RT, caspase 3 + 7 activity was further increased significantly over all other groups in all cell lines. Moreover, AS + RT resulted in significantly reduced clonogenic survival over MM + RT, which was dampened in the Bcl‐2 overexpressing lines. CONCLUSIONS To our knowledge, these data demonstrate for the first time that a Bcl‐2 specific AS oligonucleotide sensitizes prostate cancer cells to RT. p53 is not required for this effect. © 2005 Wiley‐Liss, Inc.