Downregulation of p53 promotes cell proliferation and migration and inhibits apoptosis by targeting signal transducers and activators of transcription 3 in lung cancer
ZHAO Zhenshan, LI Haiyang, ZHAO Zhenxing, DAI Dai, HAO Menghui
Department of Cardiothoracic Surgery, Kailuan General Hospital, Tangshan 063000, China
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.
赵振山, 李海洋, 赵振兴, 代岱, 郝孟辉. p53调控信号转导子和转录激活子3对肺癌细胞增殖及凋亡的影响[J]. 武警医学, 2019, 30(5): 402-405.
ZHAO Zhenshan, LI Haiyang, ZHAO Zhenxing, DAI Dai, HAO Menghui. Downregulation of p53 promotes cell proliferation and migration and inhibits apoptosis by targeting signal transducers and activators of transcription 3 in lung cancer. Med. J. Chin. Peop. Armed Poli. Forc., 2019, 30(5): 402-405.
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.
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.
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.
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.