Korean J Otolaryngol-Head Neck Surg.  2006 Apr;49(4):420-425.

The Effect of Combination Therapy with Radiation and Selective Cyclooxygenase-2 Inhibitor on Xenografted Human Oral Cavity Squamous Cell Carcinoma in Nude Mice

• Kim JH
• Park SY
• Kim HJ
• Kim KB
• Yang HS
• Lee KS
• Lee HJ
• Ji YH

Abstract

BACKGROUND AND OBJECTIVES: It is known that tumor cells over-expressing COX-2 have resistance to many anticancer treatments. Among those treatments, along with surgery and chemotherapy, radiation therapy plays a significant role in the treatment of head and neck cancer. However, radiosensitivity of each cancer varies according to cancer types. Especially, the cancer over-expressing COX-2 is reported to have higher radioresistance to radiation therapy. The purpose of this study is to evaluate the effect of selective COX-2 inhibitor when combined with the radiation therapy, and to assess the possibility of clinical application of the selective COX-2 inhibitor for radiation therapy in the head and neck cancer. MATERIALS AND METHOD: The human oral cavity squamous carcinoma cells were cultured and xenografted in 40 athymic nude mice (1 x 10(7), left thigh, subcutaneous injection) and the mice were divided into 4 groups: the control group (10 mice), the radiation therapy group (10 mice, Group A), the Meloxicam injection group (10 mice, Group B), and the combination therapy group with radiation and Meloxicam (10 mice, Group C). The tumor volume was measured on every five days during the treatment and the tumor specimen was taken for immunohistochemical staining when the treatment was finished. The mean tumor volume, the apoptosis index and the proliferation index were measured.
RESULTS
In the combination therapy group (Group C), the tumor growth rate was decreased compared to the radiation therapy group (Group A). Also, according to the result of the apoptosis index and the proliferation index measured using immunohistochemical staining, the combination therapy group presented a higher apoptosis index but a lower proliferation index than other groups.
CONCLUSION
Meloxicam, selective COX-2 inhibitor, improves the efficacy of the radiation therapy for the human oral cavity squamous carcinoma and this effect was due to apoptosis modulation by selective COX-2 inhibitor.

Keyword

Radiation therapy; Cyclooxygenase 2 inhibitors; Squamous cell carcinoma; Radiation sensitizing agents

MeSH Terms

Animals
Apoptosis
Carcinoma, Squamous Cell*
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2*
Drug Therapy
Head and Neck Neoplasms
Heterografts*
Humans*
Mice
Mice, Nude*
Mouth*
Radiation Tolerance
Radiation-Sensitizing Agents
Thigh
Tumor Burden
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Radiation-Sensitizing Agents