Therapeutic Effect of Oncolytic Herpes Simplex Virus on Induced Radioresistant Head and Neck Squamous Cell Carcinoma

Korean Journal of Head & Neck Oncology 2006;22(2):130-136.
Published online November 30, 2006.

Se-Heon Kim;Eun Chang Choi;Jin Seok Lee;Je Young Chun;Hyung Kwon Byun;Ki Jae Song;Kwang-Moon Kim

방사선 치료에 내성이 유도된 두경부 편평세포암에 대한 종양살상 헤르페스 바이러스의 유전자 치료 효과

김세헌;최은창;이진석;천제영;변형권;송기재;김광문

Abstract

Introduction ：The sensitivity of tumor cells to radiotherapy is a critical determinant of local control and po-tential cure in advanced head and neck squamous cell carcinoma(HNSCC). The emergence of radioresistant tumor cells is an obstacle to cancer therapy. Most radioresistant cells have a higher proportion of cells in the S-phase of the cell cycle and a lower apoptotic fraction than radiosensitive cells. HSV replication is increased in cells that have higher S-phase fractions. NV1066 is an oncolytic herpes simplex virus type-1 mutant. We hy-pothesized that NV1066 replication and cytotoxicity are increased in radioresistant cells. The purpose of this study is to evaluate the antitumor efficacy of NV1066 to treat radioresistant HNSCC. Methods ：Radioresistant cells were selected by treating five HNSCC cell lines with repeated conventional fractionated doses of radiation(2Gy/day), using a Cs-137 irradiator, up to a cumulative dose of 70Gy. Clonogenic cell survival and S-phase fractions were compared between radioresistant and parental radiosensitive cells. The two cell populations were then treated with NV1066 to examine viral replication, by the viral plaque assay and viral cytotoxicity. Results ：Fractionated irradiation resulted in the selection of radioresistant cells. Radioresistant cells had a higher S-phase fraction(42.9%) compared to parental cells(26.2%). NV1066 replication in radioresistant cells was 7.4times higher than in parental cells(p<0.01). Treatment with NV1066 resulted in increased cytotoxicity of 24.5% in radioresistant cells compared to parental cells(p<0.05).
Conclusion
：NV1066 showed increased viral replication and cytotoxicity in radioresistant HNSCC cell lines. These findings suggest a potential clinical application for this oncolytic viral therapy as treatment for radiore-sistant head and neck cancers.

Key Words: Gene therapy, Herpes simplex virus, Radiation, Head and neck neoplasm