Abstract:
Radiosensitization by β-elemene of Transplanted Lung Adenocarcinoma Cells in Nude Mice isRelated to the Expression of HIF-1α and CAⅨGuoquan LI1, Bingbing XIE1, Yinghai CHEN1, Xiaolong LI2, Lijuan ZOU1Correspondence to: Lijuan ZOU, E-mail: zoulijuan1963@sina.com1Department of Radiation Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China2Radiation Oncology Center, People's Liberation Army No. 323 Hospital, Xi'an 710054, ChinaThis work was supported by National Natural Science Foundation of China (No.3077064 6) and Innovative Team Project of LiaoningProvincial Education Department (No.2008T031)Abstract Objective: To establish a nude mouse model transplanted with the A549 lung adenocarcinoma cell line, to study thechange in radiosensitivity of transplanted tumors treated by β-elemene, to obtain the optimal dose to enhance the radiosensitivity oftransplanted tumors, and to investigate the association between radiosensitization by β-elemene and the expression of HIF-1α and CAⅨ. Methods: The nude mouse model transplanted with A549 lung adenocarcinoma cells was established by inoculating with a cell sus-pension. When the transplanted tumor size reached 0.8~1.0 cm3, the nude mice were randomly grouped ( 5 per group ) and the volumedoubling time was observed. The EF values were calculated and the optimal dose to enhance the radiosensitivity of transplanted tumorswas obtained. The expression of HIF-1α was assessed by RT-PCR and immunohistochemistry. The expression of CAⅨ was detected byimmunohistochemistry. Results: A nude mouse model transplanted with the A549 lung adenocarcinoma cell line was successfully estab-lished. The EF were 0.84 ( 25 mg/kg β-elemene ), 1.24 ( 45 mg/kg β-elemene ) and 2.04 ( 100 mg/kg β-elemene ) and the optimal doseto enhance radiosensitivity of the transplanted tumor was 45 mg/kg. According to RT-PCR the expression of HIF-1α was significantlyincreased in the groups treated with β-elemene or radiation alone compared with the control group ( P < 0.01 ), and there was no differ-ence between the β-elemene and radiation groups ( P > 0.05 ). According to RT-PCR the expression of HIF-1α was greatly decreased inthe co-treatment group compared with the control group ( P < 0.01 ). The results of immunohistochemistry of HIF-1α showed no differ-ence between the group treated with β-elemene alone and the control group ( P > 0.05 ), the expression of HIF-1α in the group treatedwith radiation alone was higher than that in the control group ( P < 0.05 ), and the co-treatment group had the lowest expression of allgroups ( P < 0.01 ). The immunohistochemistry results showed that the expression of CAⅨ in the group treated with radiation alone was slightly higher than that of the control group ( P > 0.05 ), while the expression in the group treated with β-elemene alone was signif-icantly higher than that of the control group ( P < 0.05 ). Immunohistochemistry also revealed that the expression of CAⅨ in theco-treatment group was the lowest of all of the groups ( P < 0.05 ). Conclusion: This study showed the optimal radiosensitization doseof β-elemene is 45 mg/kg. β-elemene combined with radiation apparently suppresses the expression of HIF-1α and CAⅨ, indicateingthat β-elemene may radiosensitize tumor cells by ameliorating hypoxic conditions in tumors. These results warrant further study.Keywords β-elemene; Transplanted tumor; Radiosensitization; HIF-1α; CAⅨ