目的 探讨p53调控信号转导子和转录激活子3(STAT3)对肺癌细胞增殖及凋亡的影响。方法 细胞分组为空白对照组、阴性对照组、p53 小干扰RNA(siRNA)组、p53 siRNA+STAT3 siRNA组,采用western blot法检测组织中p53和STAT3蛋白表达水平;采用Transwell法检测转染后体外迁移能力和侵袭能力;采用流式细胞术膜联蛋白Ⅴ/碘化丙啶(AV-PI)双染法检测转染后凋亡情况。结果 肺癌组织中p53表达水平明显下调,而STAT3表达阳性率增高,差异均有统计学意义(P<0.05)。转染p53的siRNA能显著上调肺癌细胞中STAT3的表达水平;p53 siRNA组和p53 siRNA+STAT3 siRNA组A549细胞凋亡率(17.91%±0.67%,22.51%±0.56%)、细胞的迁移速度[(55.16±6.50)μm/h,(63.30±5.98)μm/h]、穿膜细胞数(58.23±7.12,68.23±7.14),与空白对照组和阴性对照组比较,差异均有统计学意义(P<0.05)。结论 p53在肺癌中呈现低表达,p53能负向调控STAT3的表达,从而抑制其增殖和凋亡能力。
Abstract
Objective To investigate the expression of p53 in lung cancer and its effect on proliferation and apoptosis of lung cancer cells by regulating signal transducers and activators of transcription 3 (STAT3) signaling pathway.Methods Cells were divided into blank control group, negative control group, p53 small interference RNA (siRNA) group and p53 siRNA+STAT3 siRNA group. The expressions of p53 and STAT3 were detected by Western blotting. Transwell assay was used to measure cell migration and invasion, while flow cytometry using Annexin V/propidium iodide (AV-PI) double staining was adopted to detect cell apoptosis.Results The level of p53 expression in lung cancer tissues was significantly lower, while the positive rate of STAT3 expression was increased (all P<0.001). SiRNA transfected with p53 could significantly increase the expression level of STAT3 in lung cancer cells. The growth and migration ability of cells in p53 siRNA group was significantly increased, while the level of apoptosis was significantly reduced (P<0.001).Conclusion P53 shows low expressions in lung cancer, and can negatively regulate the expression of STAT3, thus inhibiting the ability of proliferation and apoptosis.
关键词
肺癌 /
p53 /
信号转导子和转录激活子3 /
细胞生长 /
细胞迁移 /
细胞凋亡
Key words
lung cancer /
p53 /
signal transducer and activator of transcription 3 /
cell growth /
cell migration /
cell apoptosis
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Ohno Y, Koyama H, Dinkel J. Lung cancer[J]. Acta Radiol Oncol, 2016, 45 (2):179-216.
[2] 孙云安, 许同宪. 心理治疗联合支气管动脉灌注化疗对老年中晚期肺癌患者生活质量及近期临床疗效的影响[J]. 河北医科大学学报, 2016, 37(9):1101-1104.
[3] Cramb S M, Baade P D, White N M, et al. Inferring lung cancer risk factor patterns through joint Bayesian spatio-temporal analysis[J]. Cancer Epidemiol, 2015, 39(3):430-439.
[4] Takiguchi Y, Sekine I, Iwasawa S, et al. Chronic obstructive pulmonary disease as a risk factor for lung cancer[J]. World J Clin Oncol, 2014, 5(4):660-666.
[5] 王 慧, 孙国平. 培美曲塞或多西他赛联合顺铂治疗晚期肺腺癌的疗效和不良反应[J]. 武警医学, 2016, 27(1):36-39.
[6] 孙桂丽, 任志红, 王大鹏,等. p53在食管癌中的研究进展[J]. 现代肿瘤医学, 2016, 24(15):2487-2490.
[7] Sui X, Kong N, Wang X, et al. JNK confers 5-fluorouracil resistance in p53-deficient and mutant p53-expressing colon cancer cells by inducing survival autophagy[J]. Sci Rep, 2014, 4(8):1255-1264.
[8] 丁聪聪, 董 悦. PBRM1和P53在子宫内膜癌中的表达及其与病理分期的相关性研究[J]. 中国妇幼保健, 2014, 29(31):5046-5048.
[9] Shahmarvand N, Nagy A, Shahryari J, et al. Mutations in the STAT family of genes in cancer.[J]. Cancer Sci, 2018, 109(4):926-933.
[10] Yu H, Lee H, Herrmann A, et al. Revisiting STAT3 signalling in cancer: new and unexpected biological functions.[J]. Nature Reviews Cancer, 2014, 14(11):736-746.
[11] Zhang H. Osimertinib making a breakthrough in lung cancer targeted therapy[J]. Onco Targets Ther, 2016,9:5489-5493.
[12] 王 弘, 王 晔, 李 倩,等. 条件性肿瘤抑制基因Unc5H4依赖P53诱导人神经母细胞瘤细胞凋亡的实验研究[J]. 中国现代医学杂志, 2014, 24(20):61-64.
[13] Zhang X, Tang J, Zhi X, et al. miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer[J]. Oncotarget, 2015, 6(3):1605-1617.
[14] Zhao D, Pan C, Sun J, et al. VEGF drives cancer-initiating stem cells through VEGFR-2/Stat3 signaling to upregulate Myc and Sox2[J]. Oncogene, 2015, 34(24):3107-3119.
[15] Shan N, Saini U, Elnaggar A C, et al. Abstract 1720: HO-3867, a selective inhibitor of stat3, suppress ovarian tumor growth and metastasis in human tissue culture and in an orthotopic mouse model[J]. Clin Cancer Res, 2015, 75(15 Supplement):1720.
[16] Liu Y, Gong W, Yang Z Y, et al. Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer[J]. Apoptosis, 2017, 22(4):544-557.
[17] Wörmann S M, Song L, Ai J, et al. Loss of P53 function activates JAK2-STAT3 signaling to promote pancreatic tumor growth, stroma modification, and gemcitabine resistance in mice and is associated with patient survival[J]. Gastroenterology, 2016, 151(1):180-193.
PDF(738 KB)
