TY - JOUR
T1 - Antisense Bcl-2 sensitizes prostate cancer cells to radiation
AU - Mu, Zhaomei
AU - Hachem, Paul
AU - Pollack, Alan
PY - 2005/12/1
Y1 - 2005/12/1
N2 - 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), PCS (p53 null), Bcl-2 stably transfected LNCaP (LNCaP-BST), and Bcl-2 stably transfected PCS (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.
AB - 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), PCS (p53 null), Bcl-2 stably transfected LNCaP (LNCaP-BST), and Bcl-2 stably transfected PCS (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.
KW - Antisense Bcl-2
KW - Apoptosis
KW - Prostate cancer
KW - Radiation
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U2 - 10.1002/pros.20303
DO - 10.1002/pros.20303
M3 - Article
C2 - 16015611
AN - SCOPUS:28744451267
SN - 0270-4137
VL - 65
SP - 331
EP - 340
JO - Prostate
JF - Prostate
IS - 4
ER -