마우스 간암에서 항암제-방사선 복합요법을 이용한 치료 효과 향상

Abstract

Backgrounds: The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. Methods: C3H/HeJ mice earing 8 mm tumors of murine hepatocarcinoma, HCa-1, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21WAF1/CIP1. Results: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gemcitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21WAF1/CIP1. Conclusion: Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.