In vivo recombinant adenovirus-mediated p53 gene therapy in a syngeneic rat model for colorectal cancer.
The p53 gene has a significant role in controlling genomic stability of cancer. The purpose of this study was to evaluate the tumor response of allograft colorectal tumor treated with Ad5CMV-p53 in a syngeneic rat model. Two weeks after the inoculation of WB-2054-M5 tumor cells in the flank of rats, rats were randomly assigned by tumor size to one of three groups (n=18 in each): phosphate buffered saline (PBS), Ad5CMV, and Ad5CMV-p53. Recombinant adenovirus or PBS was administered through intratumoral injection at three divided doses every other day for 4 weeks. Apoptosis of the tumors was evaluated using TUNEL assay. After 2 and 4 weeks of treatment, the volume (cm(3)) of tumors in PBS, Ad5CMV, and Ad5CMV-p53 was as follows: 2 week: 1.66 +/-0.43, 1.40 +/-0.47, 0.75 +/-0.26 (p<0.001), 4 week: 4.41 +/-0.88, 3.93 +/-1.86, 2.33 +/-0.51 (p<0.001). Tumor growth showed no statistically significant difference between the PBS and Ad5CMV groups (6-week vol. p=0.32). The TUNEL assay results revealed more apparent apoptotic cells in Ad5CMV-p53-treated tumors than in other groups. Growth of allograft colorectal cancer in the syngeneic rat model was significantly suppressed by intratumoral Ad5CMV-p53 gene therapy. These results demonstrate that gene replacement therapy with p53 may provide a novel modality of treatment in conjunction with other present treatments for metastatic colorectal cancer.
Baek
Jeong-Heum
JH
Department of Surgery, Gachon Medical School, Gil Medical Center, Incheon, Korea.
Agarwal
Munna L
ML
Tubbs
Raymond R
RR
Vladisavljevic
Alex
A
Tomita
Hiroshi
H
Bukowski
Ronald M
RM
Milsom
Jeffrey W
JW
Kim
Jin-Man
JM
Kwak
Jin-Young
JY
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008571:Men; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000627:therapeutic use; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000627:therapeutic use*
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53