Enhancement of Antitumor Activities of a Selective Cyclooxygenase-2 Inhibitor, Celecoxib on the Lewis Lung Carcinoma that Express Cyclooxygenase-2

COX-2 promotes carcinogenesis, tumor proliferation and growth, angiogenesis, prevention of apoptosis, immunosuppression. Selective inhibition of COX-2 activity in several animal models is associated with decrease in new vessel production in tumors, decreases in new vessel formation, and increases in tumor cell apoptosis. And selective inhibition of COX-2 activity is associated with the enhanced radiation sensitivity of tumors without appreciably increasing the effects of radiation on normal tissue. In this study, we experimented to know the effect of selective COX-2 inhibitor to inhibit tumor growth and pulmonary metastasis in animal model. The right thighs of male, 6 week old C57/BL mice were injected subcutaneous with 1 x 106 Lewis Lung Carcinoma(LLC) cells. Animals were randomized to one of six groups: no treatment(group 1), celecoxib 25mg/kg daily per oral intake alone(group 2), celecoxib 75mg/kg daily per oral intake alone(group 3), 10 Gy irradiation alone in one fraction(group 3), 10 Gy irradiation with celecoxib 25mg/kg daily per oral intake(group 5), 10 Gy irradiation with celecoxib 75mg/kg daily per oral intake(group 6). After tumor injection, tumor volume was measured three times weekly. Celecoxib feed orally every afternoon. Mice were irradiated with 4-MV photon when tumor volume of control group had reached 500 mm3. All mice were killed when the mean volume of animals of group 1 grew to 4000 mm3. The left lungs were extracted for measurement of metastatic lung nodules. COX-2 was measured by enzyme-linked immunosorbent assay(ELISA). The mean tumor volumes were 3802.2 mm3, 3814.4 mm3, 2757.6 mm3, 1942.1 mm3, 1874.3 mm3 and 1319.3 mm3 at the time of sacrifice, respectively from group 1 to group 6. The reduction of tumor volume was statistically significant, comparing between group 1 and group 3, 4, 5, and 6(p=0.0004, <0.0001, <0.0001 and <0.0001 respectively). According to celecoxib dose, the tumor volume was significantly inhibited by high dose celecoxib regardless of radiation. The lung metastasis was detected in all mice of group 1. The rates of lung metastasis from group 2 to group 6 were 100%, 75.0%, 50.0%, 87.5% and 25%. The number of metastatic lung nodules and tumor volume regardless of treatment group were well correlated(p<0.0001). The mean number of metastatic lung nodules was 2.2 at group 1, but 0.5 at group 6. There was no correlation between the size of metastatic nodules and tumor volume(p=0.2408). Treatment with radiotherapy and celecoxib 75mg/kg reduced circulating COX-2 relative to controls(p=0.0528). In conclusion, celecoxib feeding with high concentration inhibits significantly tumor growth, comparing with low concentration. In mice treated with radiotherapy and high dose celecoxib, the effect of tumor growth delay and reduction of lung metastasis were more prominent than mice treated with celecoxib or radiotherapy alone.

Author dc:creator

• 박, 원

Contributors dc:contributor

• 오, 영택
• 대학원 의학과
• 200324396

• COX-2
• 선택적 COX-2 억제제
• 방사선조사
• 종양 성장 억제
• Lewis lung carcinoma

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001859
000000001859

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1616