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rmhTNF-α抑制胃癌细胞增殖作用机制的研究
作者:张春平1  代洪生1  王津迪1  潘光敏1  高志星2  季万胜2 
单位:1. 潍坊医学院, 山东 潍坊 261053;
2. 潍坊医学院附属医院 消化内科, 山东 潍坊 261031
关键词:Δ133p53 cjun cfos 重组改构人肿瘤坏死因子-α 胃癌细胞 增殖 
分类号:R735.2
出版年·卷·期(页码):2018·46·第七期(748-750)
摘要:

目的:探讨重组改构人肿瘤坏死因子-α(rmhTNF-α)抑制人胃癌细胞增殖的作用机制。方法:将不同浓度(0、50、100、200 U·ml-1)的rmhTNF-α作用于人胃癌细胞系MKN45(干预组),采用增殖/毒性检测试剂(CCK-8)测定细胞抑制率,实时荧光定量PCR测定Δ133p53、cjun、cfos mRNA表达变化。结果:细胞抑制率干预组高于对照组(rmhTNF-α 0 U·ml-1组),且随rmhTNF-α浓度的增加而增高(P<0.05);Δ133p53 mRNA表达干预组较对照组低,且随rmhTNF-α浓度的增加而降低(P<0.05),cjun、cfos mRNA表达干预组较对照组高,且随rmhTNF-α浓度的增加而增高(均P<0.05)。Pearson相关分析显示,Δ133p53 mRNA与cjun和cfos mRNA的表达呈显著负相关(分别r=-0.954、-0.947,均P<0.01)。结论:rmhTNF-α可能是通过抑制Δ133p53表达并促进cjun、cfos表达而抑制胃癌细胞的增殖,其对Δ133p53的抑制作用可能是cjun、cfos介导的。

Objective: To investigate the mechanism of recombinant mutant human tumor necrosis factor-α(rmhTNF-α) inhibit the proliferation of human gastric cancer cell. Methods: Human gastric cancer cell lines MKN45 were treated with different concentrations(0, 50,100,200 U·ml-1) of rmhTNF-α intervention group.The cell inhibition rate was detected by proliferation/toxicity detection kit (CCK-8), and the expression of Δ133p53,cjun,cfos mRNA were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction. Results: The cell inhibition rates in the intervention group was higher than that in the control group(rmhTNF-α 0 U·ml-1 group)and it increased with the increasing of concentration of rmhTNF-α(P<0.05); the expression of Δ133p53 mRNA in the intervention group was lower than that in the control group and it decreased with the increasing of concentration of rmhTNF-α(P<0.05);the expression of cjun,cfos mRNA in the intervention group were higher than those in the control group and they increased with the increasing of concentration of rmhTNF-α(all P<0.05). Pearson correclation analysis showed the expression was negatively correlated markedly betweenΔ133p53 mRNA and cjun,cfos mRNA(r=-0.954,-0.947,respectivly,all P<0.01). Conclusion: rmhTNF may inhibit Δ133p53 expression and promote cjun,cfos expression to further inhibit gastric cancer cell proliferation,the inhibitory effect on Δ133p53 may mediated by cjun and cfos.

参考文献:

[1] TORRE L A,BRAY F,SIEGEL R L,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[2] ARSIC N,GADEA G,LAGERQVIST E L,et al.The p53 isoform Δ133p53β promotes cancer stem cell potential[J].Stem Cell Reports,2015,4(4):531-540.
[3] GONG L,CHEN G.Δ113p53/Δ133p53 converts P53 from a repressor to a promoter of DNA double-stand break repair[J].Mol Cell Oncol,2016,3(1):e1033587.
[4] SLATTER T L,HUNG N,CAMPBELL H,et al.Hyperproliferation,cancer and inflamation in mice expressing a Δ133p53-like isoform[J].Blood,2011,117(19):5166-5177.
[5] FRAGOU A,TZIMAGIORGIS G,RAGEORGOPOULOS C,et al.Increased Δ133p53 mRNA in lung carcinoma corresponds with reduction of p21 expression[J].Mol Med Rep,2017,15(4):1455-1460.
[6] SONG L,CHANG R,DAI C,et al.SORBS1 suppresses tumor metastasis and improves the sensitivity of cancer to chemotherapy drug[J].Oncotarget,2017,8(6):9108-9122.
[7] HOFSTETTER G,BERGER A,SCHUSTER E,et al.Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer[J].Br J Cancer,2011,105(10):1593-1599.
[8] AOUBALA M,MURRAY-ZMIJEWSKI F,KHOURY M P,et al.p53 directly transactivates Δ133p53α,regulating cell fate outcome in response to DNA damage[J].Cell Death Differ,2011,18(2):248-258.
[9] NUTTHASIRIKUL N,HAHNVAJANAWONG C,TECHASEN A,et al.Targeting the Δ133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoama cells[J].Int J Oncol,2015,47(6):2153-2164.
[10] BERNARD H,GARMY-SUSINI B,AINAOUI N,et al.The p53 isoform,Δ133p53α,stimulates angiogenesis and tumor progression[J].Oncogene,2013,32(17):2150-2160.
[11] HORIKAWA I,HARRIS C C.Δ133p53:A p53 isoform enriched in human stem cells[J].Cell Cycle,2017,16(18):1631-1632.
[12] BARRETT C S,MILLENA A C, KHAN S A.TGF-β effects on prostate cancer cell migration and invasion require FosB[J].Prostate,2017,77(1):72-81.
[13] TILLEY C,DEEP G,AGARWAL C,et al.Silibinin and its 2,3-Dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation[J].Mol Carcinog,2016,55(1):3-14.
[14] WEI J,NOTO J,ZAIKA E,et al.Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 respones to cellular stresses[J].Pro Nati Acad Sci U S A,2012,109(38):E2543-2550.

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