Department of Radiation Oncology,Affiliated Hosptial of Xuzhou Medical University,Xuzhou,221002,China (Li H,Huang HY,Tong SD,Zhang XJ,Wang H,Xie RL,Yao YH);Department of Radiation Oncology,Third People’s Hospital of Zhengzhou,Zhengzhou 450000,China (Zhang W);Department of Radiation Oncology,Nanjing General Hospital,Nanjing Military Region,Nanjing 210002,China (Qiu XG);Xuzhou Medical University School of Public Health,Xuzhou 221004,China (Qin ZH)
AbstractObjective To investigate the effect of liver kinase B1(LKB1) on the radiosensitivity of subcutaneous xenograft tumor of lung cancer H460 cells in nude mice. Methods Human lung cancer H460 cells were implanted into female nude mice (BALB/c-nu) to establish a subcutaneous xenograft tumor model of lung cancer. A total of 24 female nude mice in which the model was successfully established were equally and randomly divided into four groups:pEGFP-Ctrl plasmid (empty vector plasmid) group, irradiation (IR)+pEGFP-Ctrl plasmid group, pEGFP-LKB1 plasmid (overexpressing LKB1) group, and IR+pEGFP-LKB1 plasmid group. The growth of xenograft tumors was observed and the tumor inhibition rate and enhancement factor (EF) were calculated. The expression of LKB1 in each group was measured by immunohistochemistry and Western blot to analyze the relationship between LKB1 and radiosensitivity. Results Compared with the pEGFP-Ctrl plasmid group, the IR+pEGFP-Ctrl plasmid group, pEGFP-LKB1 plasmid group, and IR+pEGFP-LKB1 plasmid group showed varying degrees of inhibition of tumor growth, particularly in the IR+pEGFP-LKB1 plasmid group, and the tumor inhibition rates were 31.30%, 14.78%, and 43.48%, respectively. The EF of LKB1 in the IR+pEGFP-LKB1 plasmid group was 1.18.The immunohistochemistry and Western blot showed that LKB1 could be effectively expressed in the pEGFP-LKB1 plasmid group and IR+pEGFP-LKB1 plasmid group, but not in the other two groups. Conclusions The subcutaneous xenograft tumor model of human lung cancer H460 cells has been successfully established in nude mice. LKB1 has a radiosensitizing effect on the subcutaneous xenograft tumor of lung cancer H460 cells in nude mice.
Corresponding Authors:
Yao Yuanhu,Email:yyhxzxz@126.com
Cite this article:
Li Hao,Zhang Wei,Huang Haoying et al. Liver kinase B1 gene enhances radiosensitivity of lung cancer H460 cells:an in vivo study[J]. Chinese Journal of Radiation Oncology, 2017, 26(9): 1084-1088.
Li Hao,Zhang Wei,Huang Haoying et al. Liver kinase B1 gene enhances radiosensitivity of lung cancer H460 cells:an in vivo study[J]. Chinese Journal of Radiation Oncology, 2017, 26(9): 1084-1088.
[1] Siegel RL,Miller KD,Jemal A.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.DOI:10.3322/caac.21387. [2] Zagryazhskaya A,Gyuraszova K,Zhivotovsky B.Cell death in cancer therapy of lung adenocarcinoma[J].Int J Dev Biol,2015,59(1-3):119-129.DOI:10.1387/ijdb.150044bz. [3] Xu YM,Liao XY,Chen XW,et al. Regulation of miRNAs affects radiobiological response of lung cancer stem cells[J].BioMed Res Int,2015,2015:851841.DOI:10.1155/2015/851841. [4] Gao YJ,Ge GX,Ji HB.LKB1 in lung cancerigenesis:a serine/threonine kinase as tumor suppressor[J].Protein Cell,2011,2(2):99-107.DOI:10.1007/s13238-011-1021-6. [5] Matsumoto S,Iwakawa R,Takahashi K,et al. Prevalence and specificity of LKB1 genetic alterations in lung cancers[J].Oncogene,2007,26(40):5911-5918.DOI:10.1038/sj.onc.1210418. [6] Yao YH,Cui Y,Qiu XN,et al. Attenuated LKB1-SIK1 signaling promotes epithelial-mesenchymal transition and radioresistance of non-small cell lung cancer cells[J].Chin J Cancer,2016,35:50.DOI:10.1186/s40880-016-0113-3. [7] Amorino GP,Hercules SK,Mohr PJ,et al. Preclinical evaluation of the orally active camptothecin analog,rfs-2000(9-nitro-20(S)-camptothecin) as a radiation enhancer[J].Int J Radiat Oncol Phys,2000,47(2):503-509.DOI:10.1016/S0360-3016(00)00461-2. [8] 陈万青,郑荣寿,张思维,等.2012年中国恶性肿瘤发病和死亡分析[J].中国肿瘤杂志,2016,25(1):1-8.DOI:10.11735/j.issn.1004-0242.2016.01.A001. Chen WQ,Zheng RS,Zhang SW,et al. Report of cancer incidence and mortality in China,2012[J].China Cancer,2016,25(1):1-8.DOI:10.11735/j.issn.1004-0242.2016.01.A001. [9] Zheng H,Wang M,Wu J,et al. Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation[J].Biochem Cell Biol,2016,94(3):213-220.DOI:10.1139/bcb-2015-0139. [10] Rosell R,Karachaliou N.Lung cancer in 2014:optimizing lung cancer treatment approaches[J].Nat Rev Clin Oncol,2015,12(2):75-76.DOI:10.1038/nrclinonc.2014.225. [11] Herbst RS,Heymach JV,Lippman SM.Lung cancer[J].New Engl J Med,2008,359(13):1367-1380. [12] Li J,Yang CX,Mei ZJ,et al. Involvement of Cdc25c in cell cycle alteration of a radioresistant lung cancer cell line established with fractionated ionizing radiation[J].Asian Pac J Cancer Prev,2013,14(10):5725-5730.DOI:10.7314/ APJCP.2013.14.10.5725. [13] Jenne DE,Reomann H,Nezu JI,et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase[J].Nat Genet,1998,18(1):38-43.DOI:10.1038/ng0198-38. [14] Zhao RX,Xu ZX.Targeting the LKB1 tumor suppressor[J].Curr Drug Targets,2014,15(1):32-352 [15] Sanchez-Cespedes M.The role of LKB1 in lung cancer[J].Fam Cancer,2011,10(3):447-453.DOI:10.1007/s10689-011-9443-0. [16] Ji HB,Ramsey MR,Hayes DN,et al. LKB1 modulates lung cancer differentiation and metastasis[J].Nature,2007,448(7155):807-810.DOI:10.1038/nature06030. [17] Sun LL,Zhong DS,Wu S,et al. Establishment and gene expression profiling of LKB1 stable knockdown lung cancer cell line[J].Chin Med J (Engl),2011,124(13):2028-2032. [18] 宋耀文,韩冲,李光,等.LKB1蛋白表达与非小细胞肺癌放射敏感性的关系[J].中国医科大学学报,2013,42(8):706-709.DOI:10.3969/j.issn.0258-4646.2013.08.009. Song YW,Han C,Li G,et al. The Relationship between Expression of LKB1 Protein and Radiosensitivity of Non-small Cell Lung Cancer[J].J China Med Univ,2013,42(8):706-709.DOI:10.3969/j.issn.0258-4646.2013.08.009.