TY - JOUR
T1 - Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts
AU - Anai, Satoshi
AU - Goodison, Steve
AU - Shiverick, Kathleen
AU - Iczkowski, Kenneth
AU - Tanaka, Motoyoshi
AU - Rosser, Charles J.
PY - 2006/10
Y1 - 2006/10
N2 - The resistance of prostate cancers to radiation therapy has been linked to abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition of apoptosis. In this study, we evaluated whether the combination of the overexpression of phosphatase and tensin homolog (PTEN), a protein known to inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of athymic mice. Compared with either treatment alone, the combination of adenoviral vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited xenograft tumor growth. Median tumor size on day 48 was 1030 mm 3 in untreated controls, 656 mm3 in mice treated with radiation (5 Gy) alone, 640 mm3 in mice treated with AdPTEN alone, and 253 mm3 in mice treated with the combination (p < 0.001). Treatment was well tolerated in all cases. Combination treatment also enhanced apoptosis (p = 0.048), inhibited cellular proliferation (p = 0.005), and inhibited tumor-induced neovascularity (p = 0.030). Interestingly, this treatment increased apoptosis not only in tumor cells but also in tumor-associated endothelial cells. Together, these findings indicate that AdPTEN strongly inhibits the growth of human prostate tumors, especially when combined with radiation therapy, and that this effect is mediated by the induction of apoptosis and by the inhibition of angiogenesis and cellular proliferation.
AB - The resistance of prostate cancers to radiation therapy has been linked to abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition of apoptosis. In this study, we evaluated whether the combination of the overexpression of phosphatase and tensin homolog (PTEN), a protein known to inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of athymic mice. Compared with either treatment alone, the combination of adenoviral vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited xenograft tumor growth. Median tumor size on day 48 was 1030 mm 3 in untreated controls, 656 mm3 in mice treated with radiation (5 Gy) alone, 640 mm3 in mice treated with AdPTEN alone, and 253 mm3 in mice treated with the combination (p < 0.001). Treatment was well tolerated in all cases. Combination treatment also enhanced apoptosis (p = 0.048), inhibited cellular proliferation (p = 0.005), and inhibited tumor-induced neovascularity (p = 0.030). Interestingly, this treatment increased apoptosis not only in tumor cells but also in tumor-associated endothelial cells. Together, these findings indicate that AdPTEN strongly inhibits the growth of human prostate tumors, especially when combined with radiation therapy, and that this effect is mediated by the induction of apoptosis and by the inhibition of angiogenesis and cellular proliferation.
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U2 - 10.1089/hum.2006.17.975
DO - 10.1089/hum.2006.17.975
M3 - Article
C2 - 16984224
AN - SCOPUS:33846153618
SN - 1043-0342
VL - 17
SP - 975
EP - 984
JO - Human gene therapy
JF - Human gene therapy
IS - 10
ER -