RNAi-mediated knockdown of CAIX enhances the radiosensitivity of nasopharyngeal carcinoma cell line, CNE-2
Autor: | Gang Xu, Zihuang Li, Xiaowei Zeng, Xianming Li, Jingwen Liu, Liji Jiang, Zhuangling Li, Lin Mei |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
OncoTargets and Therapy carbonic anhydrase IX 03 medical and health sciences 0302 clinical medicine Radioresistance otorhinolaryngologic diseases medicine Pharmacology (medical) Viability assay Radiosensitivity Original Research Chemistry nasopharyngeal carcinoma Cancer Cell cycle medicine.disease radioresistance stomatognathic diseases 030104 developmental biology Oncology Nasopharyngeal carcinoma Cell culture Lipofectamine 030220 oncology & carcinogenesis Cancer research small interference RNA cell cycle |
Zdroj: | OncoTargets and therapy |
ISSN: | 1178-6930 |
Popis: | Liji Jiang,1 Gang Xu,1 Zihuang Li,1 Xiaowei Zeng,2 Zhuangling Li,1 Jingwen Liu,1 Lin Mei,2 Xianming Li1 1Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People’s Republic of China; 2The Shenzhen Key Lab of Gene and Antibody Therapy, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People’s Republic of China Abstract: Although radiotherapy remains the most powerful as well as the primary treatment modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling pathways that mediate radioresistance have been found in various kinds of cancer. However, the role of CAIX in NPC radioresistance is still unknown. In this study, we investigated the effect of CAIX silencing on sensitization to ionizing radiation in NPC by using Lipofectamine 2000, which delivers small interfering ribonucleic acid (siRNA) that targets CAIX. Results showed that Lipofectamine 2000 effectively delivered siRNA into the CNE-2 cells, which resulted in the decrease of CAIX expression and cell viability, decrease in cell proliferation and colony formation, and increase in the number of CNE-2 cells stuck in the G2/M phase of the cell cycle upon induction of ionizing radiation. Increased sensitivity of radiotherapy in CNE-2 cells under hypoxic conditions was correlated with the suppression of CAIX. Cells treated with irradiation in addition to CAIX-siRNA1 demonstrated reduced radiobiological parameters (survival fraction at 2 Gy [SF2]) compared with those treated with irradiation only, with a sensitization-enhancing ratio of 1.47. These findings suggest that CAIX can be a promising therapeutic target for the treatment of radioresistant human NPC. Keywords: carbonic anhydrase IX, small interference RNA, nasopharyngeal carcinoma, radioresistance, cell cycle |
Databáze: | OpenAIRE |
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