Improved radiosensitizing effect of the combination of etanidazole and paclitaxel for hepatocellular carcinoma in vivo.

Hepatocellular carcinoma (HCC) is one of the most critical global health issues. Potential curative therapies, including surgical resection, are offered to only a limited number of patients. Therefore, new and effective treatment strategies are required. Recently, radiotherapy with hypoxic radiosensitizers has shown promise in cancer therapy. Our previous study demonstrated that radiosensitization produced by etanidazole and paclitaxel was additive in vitro. This study was carried out to determine the synergistic effect of the two drugs in murine HCC H22 cell xenograft-bearing BALB/c mice in vivo. The morphology of the transplanted tumors was observed. The drug content in the blood and tumors of mice was measured by high-performance liquid chromatography. The radiosensitizing effect on H22 cell xenograft-bearing mice was evaluated in terms of tumor growth inhibition and survival. Expression of hypoxia inducible factor-1α (HIF-1α) was studied using immunohistochemistry. The morphological consequences on the H22 xenografts were consistent with the pathological characteristics of HCC. There was no significant difference in drug content in the blood and tumors between single drug and combination administration. The combination of the two drugs improved the radiosensitizing effect in vivo compared to single drug administration in an animal model. The changes in HIF-1α expression indirectly verified the above-mentioned results. This study may provide a new combination of radiosensitizers for HCC radiotherapy.