血红素氧合酶-1对胰腺癌细胞增殖的促进作用
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摘要
目的探讨血红素氧合酶-1(HO-1)对胰腺癌培养细胞增殖能力的影响。方法应用Real-time PCR检测胰腺癌细胞中HO-1 mRNA的表达;应用免疫荧光化学染色和Western blot检测细胞中HO-1定位表达和定量表达;应用基因转染技术构建高表达HO-1的Miapaca-2胰腺癌细胞株和低表达HO-1的Panc-1胰腺癌细胞株,并用MTT法检测胰腺癌细胞的增殖能力变化。结果胰腺癌细胞中存在HO-1的表达,通过在体外实验筛选和构建HO-1不同表达水平的胰腺癌细胞株,结果显示在人胰腺癌Panc-1细胞中,应用ZnPPIX和转染细胞Panc-1-Si-HO-1能够明显抑制胰腺癌细胞的增殖。在Miapaca-2细胞中,应用ZnPPIX明显抑制了胰腺癌细胞的增殖,而Miapaca-2-Sh-HO-1可显著促进胰腺癌细胞增殖。结论 HO-1能明显促进胰腺癌细胞的增殖能力。
Objective To study the potential effect of HO-1 on the proliferation ability of pancreatic cancer cells. Methods The mRNA expression of HO-1 in pancreatic cancer cells was detected by Real-time PCR.Immunofluorescence and Western blot analysis were made to detect the protein expression of HO-1. The gene transfection technology was used to construct a high-expression HO-1 in Miapaca-2 cells, and low-expression HO-1 in Panc-1 cells. MTT assay was carried out to examine the effect on the proliferation ability of pancreatic cancer cells. Results The expression of HO-1 existed in pancreatic cancer cells. We successfully constructed the high-and low-expression HO-1 in pancreatic cancer cell lines. The results showed that ZnPPIX and Panc-1-Si-HO-1 could significantly inhibit the proliferation ability of Panc-1 cells. In Miapaca-2 cells, ZnPPIX could significantly inhibit the proliferation ability of pancreatic cancer cells, while Miapaca-2-Sh-HO-1 could significantly promote the proliferation ability of cancer cells. Conclusion HO-1 can significantly enhance the proliferation ability of pancreatic cancer cells.
Objective To study the potential effect of HO-1 on the proliferation ability of pancreatic cancer cells. Methods The mRNA expression of HO-1 in pancreatic cancer cells was detected by Real-time PCR.Immunofluorescence and Western blot analysis were made to detect the protein expression of HO-1. The gene transfection technology was used to construct a high-expression HO-1 in Miapaca-2 cells, and low-expression HO-1 in Panc-1 cells. MTT assay was carried out to examine the effect on the proliferation ability of pancreatic cancer cells. Results The expression of HO-1 existed in pancreatic cancer cells. We successfully constructed the high-and low-expression HO-1 in pancreatic cancer cell lines. The results showed that ZnPPIX and Panc-1-Si-HO-1 could significantly inhibit the proliferation ability of Panc-1 cells. In Miapaca-2 cells, ZnPPIX could significantly inhibit the proliferation ability of pancreatic cancer cells, while Miapaca-2-Sh-HO-1 could significantly promote the proliferation ability of cancer cells. Conclusion HO-1 can significantly enhance the proliferation ability of pancreatic cancer cells.
引文
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[14] PISHVAIAN MJ,BRODY JR.Therapeutic implications of molecular subtyping for pancreatic cancer[J].Oncology (Williston Park),2017,31(3):159-166,168.
[15] REN QG,YANG SL,HU JL,et al.Evaluation of HO-1 expression,cellular ROS production,cellular proliferation and cellular apoptosis in human esophageal squamous cell carcinoma tumors and cell lines[J].Oncol Rep,2016,35(4):2270-2276.
[2] LIU Q,LIAO Q,ZHAO Y.Chemotherapy and tumor microenvironment of pancreatic cancer[J].Cancer Cell Int,2017,17(1):68.
[3] OTTERBEIN LE,CHOI AM.Heme oxygenase:Colors of defense against cellular stress[J].Am J Physiol Lung Cell Mol Physiol,2000,279(6):L1029-1037.
[4] JAZWA A,STOSZKO M,TOMCZYK M,et al.HIF-regulated HO-1 gene transfer improves the post-ischemic limb recovery and diminishes TLR-triggered immune responses—Effects modified by concomitant VEGF overexpression[J].Vascul Pharmacol,2015,71(4):127-138.
[5] HEEBA GH,HAMZA AA,HASSANIN SO.Induction of heme oxygenase-1 with hemin alleviates cisplatin-induced reproductive toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line[J].Toxicol Lett,2016,264(12):38-50.
[6] JO EJ,PARK SJ,KIM BC.Propyl gallate sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting heme oxygenase-1 for TRC8-mediated degradation[J].Eur J Pharmacol,2016,788(10):321-327.
[7] SCHWER CI,GUERRERO AM,HUMAR M,et al.Heme oxygenase-1 inhibits the proliferation of pancreatic stellate cells by repression of the extracellular signal-regulated kinase1/2 pathway[J].J Pharmacol Exp Ther,2008,327(3):863-871.
[8] BERBERAT PO,DAMBRAUSKAS Z,GULBINAS A,et al.Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment[J].Clin Cancer Res,2005,11(10):3790-3798.
[9] SUNAMURA M,DUDA DG,GHATTAS MH,et al.Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer[J].Angiogenesis,2003,6(1):15-24.
[10] BAKER H.Surveillance benefit for pancreatic cancer in high-risk individuals[J].Lancet Oncol,2016,17(6):e227.
[11] LONG J,LUO GP,XIAO ZW,et al.Cancer statistics:current diagnosis and treatment of pancreatic cancer in Shanghai,China[J].Cancer Lett,2014,346(2):273-277.
[12] O'DWYER PJ.Locally advanced pancreatic cancer:Maybe not so local[J].Lancet Oncol,2016,17(6):694-695.
[13] GUNGOR C,HOFMANN BT,WOLTERS-EISFELD G,et al.Pancreatic cancer[J].Br J Pharmacol,2014,171(4):849-858.
[14] PISHVAIAN MJ,BRODY JR.Therapeutic implications of molecular subtyping for pancreatic cancer[J].Oncology (Williston Park),2017,31(3):159-166,168.
[15] REN QG,YANG SL,HU JL,et al.Evaluation of HO-1 expression,cellular ROS production,cellular proliferation and cellular apoptosis in human esophageal squamous cell carcinoma tumors and cell lines[J].Oncol Rep,2016,35(4):2270-2276.