Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase

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Abstract

The resistance of non-small cell lung cancer (NSCLC) to radiation is the major reason for radiotherapy failure of this kind cancer. Currently, there is no effective radiosensitizer in clinical use. Artemisinin and its derivates enhance radiotherapeutic effect in some kinds of tumors; however, whether artemisinin and its derivates can enhance the radiosensitivity of NSCLC remains unknown. Therefore, in the present experiments, artemisinin and its derivatives were firstly screened for their radiosensitization on NSCLC A549 (A549) cells and then the possible mechanisms were investigated. Our results showed that artesunate enhance radiosensitivity of A549 cells in vitro among artemisinin and its derivatives, and artesunate combined with local radiotherapy retarded the tumor growth in nude tumor xenografts; the inhibition produced by 30 mg/kg of artesunate was 74.6%. The results on the possible mechanisms showed artesunate increased the NO level within irradiated A549 cells. Artesunate didn't induce apoptosis of irradiated cells but induced G2/M arrest. The induced G2/M arrest was related to down-regulated cyclin B1 mRNA expression. Taken together, artesunate exhibited potent radiosensitivity against human A549 cells in vitro and in vivo, probably via NO signal transduction pathway to induce cell cycle arrest at G2/M phase. Therefore, artesunate should be further investigated as a radiosensitizer in clinical application.

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