施倩
·基礎(chǔ)研究·
IRF-2在胰腺癌中的功能及其對(duì)胰腺癌細(xì)胞化療敏感性的影響
施倩
目的 分析與探討IRF-2在胰腺癌中的功能及其對(duì)胰腺癌細(xì)胞化療敏感性的影響。方法采用METT檢測(cè)吉西他濱對(duì)胰腺癌細(xì)胞株MIAPaCa-2與PANC-1的半數(shù)計(jì)量,對(duì)以上兩種細(xì)胞對(duì)胰腺癌細(xì)胞化療敏感程度加以了解,選擇較為耐藥的細(xì)胞對(duì)IRF-2對(duì)胰腺癌細(xì)胞化療敏感性的影響進(jìn)行進(jìn)一步探討。結(jié)果MIAPaCa-2與PANC-1細(xì)胞中均存在IRF-2基因表達(dá),PANC-1細(xì)胞中比MIAPaCa-2高,吉西他濱對(duì)MIAPaCa-2細(xì)胞半數(shù)有效劑量明顯低于PANC-1,P<0.05,藥物作用72h后,干擾IRF-2表達(dá)細(xì)胞IC50值低于PANC-1對(duì)照細(xì)胞,由此表明,IRF-2基因表達(dá)下調(diào)后,提升了PANC-1細(xì)胞對(duì)胰腺癌細(xì)胞化療敏感性。結(jié)論研究表明,IRF-2干擾技術(shù)特異性能夠有效提升PANC-1胰腺癌細(xì)胞對(duì)吉西他濱的化療敏感性。
胰腺癌,IRF-2,吉西他濱,化療敏感性
胰腺癌是具有較高惡性程度的一種腫瘤,且具有較高死亡率,五年的生存率在5%以下[1]。固然最近幾年來(lái)診斷和醫(yī)治技巧賡續(xù)進(jìn)步,但患者生計(jì)狀態(tài)仍不容樂(lè)觀。本研究主要分析與探討IRF-2在胰腺癌中的功能及其對(duì)胰腺癌細(xì)胞化療敏感性的影響,具體報(bào)告如下:
1.1 一般資料
所選藥物為吉西他濱(江蘇豪森醫(yī)藥公司生產(chǎn)),0.2g/支,藥物生產(chǎn)批號(hào):110807。所選細(xì)胞與動(dòng)物為下調(diào)IRF-2表達(dá)的PANC-1與MIAPaCa-2細(xì)胞,雄性裸鼠,平均周齡為(5.0±1.0)周。
1.2 方法
在96孔板中均勻平鋪細(xì)胞,過(guò)夜鐵壁,分別用0、0.1、1、10及100μg/ml濃度的吉西他濱處理細(xì)胞。所有濃度均進(jìn)行72h的處理,將三個(gè)平行孔制作于各時(shí)間點(diǎn)中,最后采用MTT檢測(cè)細(xì)胞所用的OD值,對(duì)比各自沒(méi)有處理的對(duì)照組,對(duì)吉西他濱IC50(半數(shù)有效濃度)進(jìn)行計(jì)算,計(jì)算公式為:IgIC50=Xm-I(P-(3-Pm-Pn)/4)(I表示最大濃度/相臨濃度;Xm表示Ig最大濃度;P表示陽(yáng)性反應(yīng)率之和;Pn表示最小陽(yáng)性反應(yīng)率;Pm表示最大陽(yáng)性反應(yīng)率)[2]。
1.3 統(tǒng)計(jì)學(xué)處理
2.1 胰腺癌細(xì)胞系中IRF-2的表達(dá)
MIAPaCa-2與PANC-1細(xì)胞中均存在IRF-2基因表達(dá),PANC-1細(xì)胞中比MIAPaCa-2高,吉西他濱對(duì)MIAPaCa-2細(xì)胞半數(shù)有效劑量低于PANC-1,P<0.05,藥物作用72h后,干擾IRF-2表達(dá)細(xì)胞MIAPaCa-2的IC50值(5.7±1.1)μg/ml低于PANC-1對(duì)照細(xì)胞(16.6±2.0)μg/ml,由此表明,IRF-2基因表達(dá)下調(diào)后,提升了PANC-1細(xì)胞對(duì)胰腺癌細(xì)胞化療敏感性。由此可見(jiàn),MIAPaCa-2細(xì)胞和PANC-1細(xì)胞對(duì)比,MIAPaCa-2細(xì)胞對(duì)吉西他濱化療的敏感性比較強(qiáng)。
2.2 下調(diào)IRF-2表達(dá)對(duì)胰腺癌細(xì)胞化療敏感性的影響
PANC-1 si con細(xì)胞的半數(shù)有效濃度值為(16.4±1.4)μg/ml,而PANC-1 si2#細(xì)胞的半數(shù)有效濃度值為(9.5±1.3)μg/ml,兩者差異明顯,P<0.05,具有統(tǒng)計(jì)學(xué)意義。
雖然近些年在綜合治療胰腺癌方面取得大量進(jìn)展,也出現(xiàn)了很多新化療藥物,然而,依舊沒(méi)有解決腫瘤細(xì)胞耐藥問(wèn)題?,F(xiàn)階段,應(yīng)該研制新方法以增加對(duì)化療治療的敏感性,這樣才能提高胰腺癌患者在治療過(guò)程中的生存時(shí)間。IRF-2(干擾素調(diào)控因子2)是在4號(hào)染色體中定位的一個(gè)長(zhǎng)臂基因,為干擾素調(diào)控因子范疇。在干擾素信號(hào)轉(zhuǎn)導(dǎo)通路與免疫調(diào)節(jié)中,IRF-2發(fā)揮著極為重要的作用,此外,更多研究發(fā)現(xiàn),IRF-2參與了腫瘤的發(fā)生與發(fā)展,對(duì)細(xì)胞周期與凋亡具有調(diào)控作用[2]。而且RANC-1中,對(duì)IRF-2基因表達(dá)進(jìn)行不斷下調(diào),會(huì)導(dǎo)致吉西他濱對(duì)胰腺癌細(xì)胞的半數(shù)有效濃度值的下降,增加了胰腺癌細(xì)胞化療敏感性。由此可見(jiàn),IRF-2干擾技術(shù)特異性能夠有效提升PANC-1胰腺癌細(xì)胞對(duì)吉西他濱的化療敏感性。
[1]崔磊.IRF-2在胰腺癌中的功能及其對(duì)胰腺癌細(xì)胞化療敏感性的影響[D].上海:復(fù)旦大學(xué),2012.
[2]易小平,龍學(xué)穎,劉慧,等.抑制X染色體連鎖的凋亡抑制蛋白(XIAP)和Survivin表達(dá)對(duì)胰腺癌Panc-1細(xì)胞增殖及化療敏感性的影響[J].北京大學(xué)學(xué)報(bào),2013(2):10-11.
IRF-2 in Pancreatic Function and Its Chemosensitivity of Pancreatic Cancer Cells
SHI Qian,The Yellow River Water Conservancy Committee of the Central Hospital,Zhengzhou 450000,China
ObjectiveThe purpose of the analysis and discussion of IRF-2 in pancreatic function and its chemosensitivity of pancreatic cancer cells.MethodsTo detect METT gemcitabine in pancreatic cancer cell lines MIAPaCa-2 and PANC-1 half measurement of these two cells to understand the sensitivity of chemotherapy for pancreatic cancer cells,select the cells more resistant to IRF-2 in pancreatic cancer cells chemosensitivity be further explored.ResultsMIAPaCa-2 and PANC-1 cells exist in IRF-2 gene expression,PANC-1 cells than MIAPaCa-2 high,gemcitabine MIAPaCa-2 cells median effective dose was significantly lower than PANC-1,P<0.05,drugs for 72h after interference IRF-2-expressing cells IC50 values below PANC-1 control cells,which showed that downregulation of IRF-2 gene,to enhance the PANC-1 cells to pancreatic cancer cell sensitivity to chemotherapy.ConclusionThe study shows that,IRF-2 specific interference technology can effectively enhance chemosensitivity PANC-1 pancreatic cancer cells to gemcitabine.
Pancreatic cancer,IRF-2,Gemcitabine chemosensitivity
作者單位:450000鄭州市黃河水利委員會(huì)黃河中心醫(yī)院
R736
B
1674-9308(2015)12-0119-01
10.3969/j.issn.1674-9308.2015.12.097