血小板对人肺癌细胞株A549凋亡的影响及机制初探
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摘要
目的探讨血小板(PLT)对肺癌细胞株A549的影响及其可能的机制。方法通过流式细胞术检测PLT对A549细胞的凋亡作用;Westernblot检测PLT和A549细胞共培养后A549细胞中ERK1/2、JNK、p-ERK、p-JNK、MMP–2、M M P–9、 B c l–2、 B a x蛋白的表达情况。结果应用流式细胞术的检测结果发现,血小板抑制A 549细胞的凋亡并能阻止化疗药物吉西他滨诱导的A549细胞凋亡。Westernblot结果显示PLT和A549细胞共培养48h后,A549细胞中ERK1/2、JNK、p-E R K、 p-J N K、 M M P-2、 M M P-9、 B c l-2蛋白表达明显增加, B a x蛋白表达明显降低。结论血小板可增加A 549细胞中ERK1/2、JNK、p-ERK、p-JNK磷酸化,增加MMP-2、MMP-9和Bcl-2蛋白的表达;降低Bax蛋白表达,并抑制肺癌细胞株A549的凋亡。血小板可抑制A549细胞的凋亡,且与血小板的浓度呈正相关。
Objective To study the impact of platelet on tumor cell apoptosis which is associated with resistance of lung cancer cells to chemotherapy.Methods Flow cytometry was performed to detect the apoptosis of A549 induced by PLT. The expression of ERK1/2,JNK,p-ERK,p-JNK,MMP 2,MMP-9,the Bcl-2,Bax was examined by Western blotting after co-culture of PLT with A549 cells. Results The expression of ERK1/2,JNK,p-ERK,p-JNK,MMP-2,MMP-9,and Bcl-2 was significantly upregulated while Bax was decreased after 48 h cultrue. ConclusionsPlatelets facilitated migration of A549 cells in vitro,which was positively correlated with the platelet concentrations. Platelets increased the phosphorylation of ERK1/2,JNK,p-ERK,p-JNK; MMP-2 and the expression of MMP-2,MMP-9,and Bcl-2,but decreased the expression of Bax protein and inhibited the apoptosis of lung adenocarcinoma cells.
Objective To study the impact of platelet on tumor cell apoptosis which is associated with resistance of lung cancer cells to chemotherapy.Methods Flow cytometry was performed to detect the apoptosis of A549 induced by PLT. The expression of ERK1/2,JNK,p-ERK,p-JNK,MMP 2,MMP-9,the Bcl-2,Bax was examined by Western blotting after co-culture of PLT with A549 cells. Results The expression of ERK1/2,JNK,p-ERK,p-JNK,MMP-2,MMP-9,and Bcl-2 was significantly upregulated while Bax was decreased after 48 h cultrue. ConclusionsPlatelets facilitated migration of A549 cells in vitro,which was positively correlated with the platelet concentrations. Platelets increased the phosphorylation of ERK1/2,JNK,p-ERK,p-JNK; MMP-2 and the expression of MMP-2,MMP-9,and Bcl-2,but decreased the expression of Bax protein and inhibited the apoptosis of lung adenocarcinoma cells.
引文
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2 Kojima S,Nishioka C,Chi S,et al.In vitro studies on the role of recombinant human soluble thrombomodulin in the context of retinoic acid mediated APL differentiation syndrome[J].Leukemia Res,2017,63(12):1-9.
3 Brockmann M A,Giese A,Muller K,et al.Preoperative thrombocytosis predicts poor survival in patients with glioblastoma[J].Neuro Oncology,2007,9(3):335-342.
4 Pietramaggiori G,Scherer S S,Cervi D,et al.Tumors stimulate platelet delivery of angiogenic factors in vivo:An unexpected benefit[J].Am J Pathol,2008,173(6):1609-1616.
5 Sujitha S,Rasool M.MicroRNAs and bioactive compounds on TLR/MAPK signaling in rheumatoid arthritis[J].Clinica Chimica Acta,2017,473(10):106-115.
6 Yang Y,Li X,Du J,et al.Involvement of microRNAs-MMPs-E-cadherin in the migration and invasion of gastric cancer cells infected with Helicobacter pylori[J].Exp Cell Res,2018,367(2):196-204.
7 Labelle M,Begum S,Hynes R O.Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis[J].Cancer Cell,2011,20(5):576-590.
8 Steller E J,Raats D A,Koster J,et al.PDGFRB promotes liver metastasis Formation of mesenchymal-like colorectal tumor cells[J].Neoplasia,2013,15(2):204-207.
9 Park H B,Yang J H,Chung K H.Characterization of the cytokine profile of platelet rich plasma(PRP)and PRP-induced cell proliferation and migration:upregulation of matrix metalloprotein-1and 9 in HaCaT cells[J].Korean J Hematol,2011,46(4):265-273.
10 Dahesvsky O,Varon D,Brill A.Platelet-derived microparticles promote invasiveness of prostate cancer cells via upregulation of MMP-2 production[J].Int J Cancer,2009,124(4):1773-1777.
11 Martinek I,Haldar K,Gaitskell K,et al.DNA-repair pathway inhibitors for the treatment of ovarian cancer[J].Cochrane Database Syst Rev,2010,(6):CD007929.
12 Dankova Z,Zubor P,Grendar M,et al.Association of single nucleotide polymorphisms in FGF-RAS/MAP signalling cascade with breast cancer susceptibility[J].Gen Physiol Biophys,2017,36(5):565-572.
13 Chaiwangyen W,Ospina-Prieto S,Morales-Prieto D M,et al.Oncostatin M and leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells[J].Reprod Fertil Dev,2014,28(5):608-617.
14 Herszenyi L,Hritz I,Pregun I,et al.Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events.in esophageal carcinogenesis[J].World J Gastroenterol,2007,13(5):676-682.
15 Jiang B,Chen J,Yuan W,et al.Platelet-derived growth factor-Dpromotes colorectal cancer cell migration,invasion and proliferation by regulating Notch1 and matrix metalloproteinase-9[J].Oncology Letters,2018,15(2):1573-1579.
16 Min KW,Kim D H,Do S I,et al.Expression patterns of stromal MMP-2 and tumoural MMP-2 and-9 are significant prognostic factors in invasive ductal carcinoma of the breast[J].APMIS,2014,122(12):1196-1206.