Enhanced radiosensitizing by sodium glycididazole in a recurrent esophageal carcinoma tumor model
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Peipei Wu1,2,*, Jing Liu1,*, Xiaorong Sun3, Xiaolin Li1, Ligang Xing1 and Jinming Yu1
1Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China
2Department of Oncology, Jining No.1 People’s Hospital, Jining 272011, Shandong, China
3Department of Radiology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China
*These authors have contributed equally to this work
Ligang Xing, email: [email protected]
Keywords: esophageal cancer, sodium glycididazole, radiosensitizer, tumor bed effect, hypoxia
Received: December 15, 2016 Accepted: June 05, 2017 Published: July 10, 2017
Re-irradiation is challenging for esophageal cancer patients with local-regional recurrence after initial radiotherapy. The purpose of this study is to establish a recurrent esophageal tumor model and investigate radiosensitizing effects of sodium glycididazole (CMNa). Tumor models were established by pre-irradiation (0 Gy, 10 Gy or 20 Gy) to the right hind leg of the nude mice 24 hours before tumor transplantation (ECA109 human esophageal carcinoma cells). Tumor growth curves were analyzed. Hypoxic microenvironment was exhibited in tumor frozen slides stained for pimonidazole, Hoechst 33342, hematoxylin-eosin and CD34. Mice bearing primary (0 Gy pre-irradiation) and recurrent (10 Gy pre-irradiation) tumors were randomized into control (no treatment), radiation (30 Gy in 3 weekly fractionations), or radiation combined with CMNa (1 mmol/kg i.p. injected 60 min before radiation) respectively. The data showed tumors from 10 Gy and 20 Gy pre-irradiated sites grew significantly slower than those in the 0 Gy pre-irradiated group. The recurrent xenograft tumors showed increased necrotic fractions, decreased micro-vascular density, increased pimonidazole-positive fraction, and decreased Hoechst-positive fraction. In the primary xenograft tumors, CMNa adding to radiation did not lead to significant tumor growth delay than radiation alone. However, for the recurrent tumor model, the growth rate was remarkably reduced as CMNa combined with radiation as comparison with radiation alone. In conclusion, the recurrent esophageal xenograft model with tumor bed effect was successfully established characterized by slow growth, increased hypoxia fraction and decreased blood flow. Significant radiosensitization by CMNa was demonstrated in the recurrent model.
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