摘要
Background The failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that 125I labeled triple-helix forming oligonucleotide （TFO） against the androgen receptor gene inhibits androgen receptor expression and cell proliferation of LNCaP prostate cancer cells in vitro. This study aimed at exploring the effects of the 125I-TFO on prostate tumor growth in vivo using a nude mouse xenograft model. Methods TFO was labeled with 125I by the iodogen method. Thirty-two nude mice bearing LNCaP xenograft tumors were randomized into 4 groups and were intratumorally injected with 125I-TFO, unlabeled TFO, Na125I and normal saline. Tumor size was measured weekly. The tumor growth inhibition rate （RI） was calculated by measurement of tumor weight. The expression of the androgen receptor gene was performed by RT-PCR and immunohistochemical study. The prostate specific antigen （PSA） serum levels were measured by enzyme linked immunosorbent assay. The tumor cell apoptosis index （AI） was detected by TUNEL assay. Results Tumor measurements showed that tumor development was significantly inhibited by either 125I-TFO or TFO, with tumor RIs of 50.79% and 32.80% respectively. 125I-TFO caused greater inhibition of androgen receptor expression and higher AIs in tumor tissue than TFO. Both the tumor weight and the PSA serum levels in 125I-TFO treated mice （（0.93±0.15） g and （17.43±1.85） ng/ml, respectively） were significantly lower than those （（1.27±0.21） g and （28.25±3.41） ng/ml, respectively） in TFO treated mice （all P〈0.05）. Na 125I did not significantly affect tumor growth and androgen receptor expression in tumor tissue. Conclusions The 125I-TFO can effectively inhibit androgen receptor expression and tumor growth of human prostate cancer xenografts in vivo. The inhibitory efficacy of 125I-TFO is more potent than that of TFO, providing a reference for future studies of antigen radiotherapy.
Background The failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that 125I labeled triple-helix forming oligonucleotide （TFO） against the androgen receptor gene inhibits androgen receptor expression and cell proliferation of LNCaP prostate cancer cells in vitro. This study aimed at exploring the effects of the 125I-TFO on prostate tumor growth in vivo using a nude mouse xenograft model. Methods TFO was labeled with 125I by the iodogen method. Thirty-two nude mice bearing LNCaP xenograft tumors were randomized into 4 groups and were intratumorally injected with 125I-TFO, unlabeled TFO, Na125I and normal saline. Tumor size was measured weekly. The tumor growth inhibition rate （RI） was calculated by measurement of tumor weight. The expression of the androgen receptor gene was performed by RT-PCR and immunohistochemical study. The prostate specific antigen （PSA） serum levels were measured by enzyme linked immunosorbent assay. The tumor cell apoptosis index （AI） was detected by TUNEL assay. Results Tumor measurements showed that tumor development was significantly inhibited by either 125I-TFO or TFO, with tumor RIs of 50.79% and 32.80% respectively. 125I-TFO caused greater inhibition of androgen receptor expression and higher AIs in tumor tissue than TFO. Both the tumor weight and the PSA serum levels in 125I-TFO treated mice （（0.93±0.15） g and （17.43±1.85） ng/ml, respectively） were significantly lower than those （（1.27±0.21） g and （28.25±3.41） ng/ml, respectively） in TFO treated mice （all P〈0.05）. Na 125I did not significantly affect tumor growth and androgen receptor expression in tumor tissue. Conclusions The 125I-TFO can effectively inhibit androgen receptor expression and tumor growth of human prostate cancer xenografts in vivo. The inhibitory efficacy of 125I-TFO is more potent than that of TFO, providing a reference for future studies of antigen radiotherapy.
基金
This study was supported by a grant from the Natural Science Foundation of Guangdong Province, China （No. 5001697）.
