| Xiao Guohui,Li Na,Wei Yan,Xu Hui,Peng Jin,Zhou Fuxiang.Mitochondrial dysfunction-induced expression of TGF-β1 pathway promoting epithelial-mesenchymal transition in pancreatic cancer cells after X-ray exposure[J].Chinese Journal of Radiological Medicine and Protection,2021,41(6):407-412 |
| Mitochondrial dysfunction-induced expression of TGF-β1 pathway promoting epithelial-mesenchymal transition in pancreatic cancer cells after X-ray exposure |
| Received:January 27, 2021 |
| DOI：10.3760/cma.j.issn.0254-5098.2021.06.002 |
| KeyWords:X-rays Mitochondria Pancreatic cancer Migration TGF-β1 |
| FundProject:国家自然科学基金（81903136） |
| Author Name | Affiliation | E-mail | | Xiao Guohui | Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behavior of Hubei Province, Clinical Cancer Study Center of Hubei Province, Peritoneal Cancer Clinical Medicine Research Center, Wuhan 430071, China | | | Li Na | Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behavior of Hubei Province, Clinical Cancer Study Center of Hubei Province, Peritoneal Cancer Clinical Medicine Research Center, Wuhan 430071, China | | | Wei Yan | Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behavior of Hubei Province, Clinical Cancer Study Center of Hubei Province, Peritoneal Cancer Clinical Medicine Research Center, Wuhan 430071, China | | | Xu Hui | Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behavior of Hubei Province, Clinical Cancer Study Center of Hubei Province, Peritoneal Cancer Clinical Medicine Research Center, Wuhan 430071, China | | | Peng Jin | Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behavior of Hubei Province, Clinical Cancer Study Center of Hubei Province, Peritoneal Cancer Clinical Medicine Research Center, Wuhan 430071, China | | | Zhou Fuxiang | Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behavior of Hubei Province, Clinical Cancer Study Center of Hubei Province, Peritoneal Cancer Clinical Medicine Research Center, Wuhan 430071, China | happyzhoufx@sina.com |
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| Abstract:: |
| Objective To investigate epithelial-mesenchymal transition and to explore the effects of mitochondrial dysfunction and increased expression of TGF-β1 pathway on epithelial-mesenchymal transition (EMT) in pancreatic adenocarcinoma after X-ray irradiation. Methods Split-dose irradiations of total 40 Gy (2 Gy×20 and 4 Gy×10) of 6 MV X-rays were performed on PATU1 988 t cells. The migration of the cells were examined through transwell filter chambers. Real-time PCR was adopted to detect the expression of EMT-related factors E-cadherin, Vimentin, N-cadherin, and MMPs (MMP2 and MMP9), critical subunits of mitochondrial complex I, and TGF-β1. The expression of EMT-related factors and content of TGF-β1 was detected after carbonylcyanide-m-chlorophenylhydrazone(CCCP) treatment. Meanwhile, the migration potential of pancreatic cells was detected after small interfering RNA (siRNA) knockdown of the expression of TGF-β1. Results After irradiation, the migration capacities of the cancer cells increased (t=21.90, 35.64, P<0.05). The expression of N-cadherin (t=4.42, 4.77, P<0.05), Vimentin (t=4.57, 3.02,P<0.05), MMP2 (t=7.27, 26.08, P<0.05), and MMP9 (t=13.26, 7.29, P<0.05) all increased, while the expression of E-cadherin deceased (t=8.37, 6.77, P<0.05). The expression of TGF-β1 (t=90.49, 35.17, P<0.05) increased. The expression of TGF-β1 decreased with small interfering RNA, which paralleled the inhibition of the epithelial-mesenchymal transition and migration (t=38.66, 11.54, P<0.05). Mitochondrial dysfunction was reflected by the decline in the membrane potential (t=6.94, 29.71, P<0.05) and complex-related subunits. The expression of TGF-β1 (t=47.93, P<0.05) and EMT-related factors further increased after mitochondrial function was destroyed (t=16.51,P<0.05). Conclusions Radiation-induced mitochondrial dysfunction can increase the expression of TGF-β1, which promotes epithelial-mesenchymal transition, and result in the migration of pancreatic cancer cell line. |
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