Abstract
Radiotherapy is one of the major therapeutic modalities for the treatment of oral cancer. However, the existence of radioresistant cells would be linked to the failure of tumor radiotherapy. In order to develop more effective tumor radiotherapy, we have to understand the feature of radioresistant cells. For this purpose, clinically relevant radioresistant (CRR) cell line, SAS-R which can continue to proliferate with daily exposure to 2 Gy of X-rays, was obtained from human oral cancer SAS by the exposure to step-wise increase of fractionated X-rays. Recently, many studies suggested that angiogenesis is one of the most important factors for tumor growth and inhibition of angiogenesis is effective to tumor treatment. We observed more number of vessels in SAS-R tumors inoculated in the back of nude mice than SAS tumors. These observations prompted us to examine whether RAD001, a newly-developed angiogenesis inhibitor, is effective for the treatment of CRR tumors or not. Combination of fractionated 2 Gy of X-rays and RAD001 was more effective to reduce the tumor volume than either radiation or RAD001 alone. Interestingly, combination treatment revealed more rapid reduction of SAS-R tumors than SAS tumors. In addition, in vitro study showed that SAS-R secreted higher amount of VEGF than SAS. Our results suggest that radiotherapy with RAD001 is effective for the treatment of radioresistant oral cancer.
