[Effects of anti-gene and antisense therapeutics on human prostate cancer xenograft in nude mice].
OBJECTIVE
To investigate the effects of triple-helix forming oligonucleotide (TFO) and antisense oligonucleotide (ASO) on androgen receptor (AR) expression and tumor growth of human prostate cancer xenografts in nude mice.


METHODS
Thirty-two nude mice were inoculated with human prostate cancer cells of the line LNCaP-C4-2 were randomized into 4 equal groups: TFO treatment group, undergoing intra-tumor injection of TFO at the dose of 25 mgxkg(-1)x(2d)(-1) for 14 times, ASO treatment group, undergoing intra-tumor injection of ASO at the same dose for 14 times, SCO group, undergoing intra-rumor injection of sequence control oligonucleotide (SCO) at the same dose for 14 times, and control group. The body weight and xenograft tumor volume of the nude mice were monitored during the therapy. 28 days later venous blood samples were collected to measure the level of prostate specific antigen (PSA) by radioimmunoassay and then the mice were killed with their tumors taken out to measure the weight, and RT-PCR, immunohistochemistry, and radioligand binding assay were used to detect the AR gene mRNA and protein expression in the tumor tissues.


RESULTS
By the end of experiment the volumes and weights of tumor of the ASO and ASO groups were all significantly lower than those of the control group (all P < 0.01) with the inhibition rates of 67.55% and 41.06% respectively, and the volumes and weights of tumor of the TFO group were all significantly lower than those of the ASO group (all P < 0.05). The tumor weight and AR expression levels of TFO group were significantly lower than those of ASO group (P < 0.05). The serum PSA level of TFO group was (6.6 +/- 1.0) ng/ml, significantly lower than that of the ASO group [(19.8 +/- 3.7) ng/ml, P < 0.05]. The mRNA and protein expression levels of AR of the TFO group were significantly lower than those of the other groups (all P < 0.05). There were no significant differences in all the above mentioned markers between the SCO and control groups (all P > 0.05).


CONCLUSIONS
TFO shows significantly higher inhibitory effect on AR expression and tumor growth of human prostate cancer xenograft than ASO, and is a promising agent for prostate cancer gene therapy.
Zhang
Yong
Y
Department of Nuclear Medicine, Third Affiliated Hospital of SUN Yat-sen University, Guangzhou 510630, China.
Ma
Yi
Y
Lu
Han-ping
HP
Zhou
Xiang-fu
XF
Xie
Yao
Y
Gao
Jin-hui
JH
Liang
Chang-sheng
CS
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009841:Oligonucleotides / Q000008:administration & dosage / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011944:Receptors, Androgen / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011944:Receptors, Androgen