紫杉醇对人胆管癌QBC939细胞wnt/β-catenin信号通路基因和蛋白表达的影响
Effects of Paclitaxel on Gene and Protein Expression of wnt/β-catenin Signaling Pathway in Cholangiocarcinoma Cell Line QBC939
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摘要: 目的 探讨紫杉醇对人胆管癌QBC939细胞wnt/β-catenin信号通路中基因和蛋白表达的影响.方法常规培养QBC939细胞,Westernblot检测0.1、1、10 nmol/L紫杉醇组和对照组细胞中β-catenin蛋白的表达量,Q-PCR检测10 nmol/L紫杉醇组和对照组细胞中P53和C-jun基因表达,干预时间均为24 h.结果 与对照组比较,紫杉醇各组β-catenin蛋白含量均有下降,当紫杉醇浓度达到10 nmol/L时,β-catenin蛋白表达明显降低(P<0.05).与对照组比较,经10 nmol/L的紫杉醇干预24 h后,P53基因表达上升(P<0.05),而C-jun基因表达下降(P<0.05).结论 紫杉醇通过抑制QBC939细胞内β-catenin蛋白表达,阻断Wnt信号通路,诱导抑癌基因P53的表达,降低癌基因C-jun的表达.Abstract: Objective To explore the effects of paclitaxel on gene and protein expression of wnt/β-catenin signaling pathway in cholangiocarcinoma cell line QBC939. Methods Western blot was used to detectβ-cateninprotein expression level in 0.1, 1, 10 nmol/L paclitaxel groups and control group for 24 h. q-PCR was used to detect c-jun and p53 mRNA expression level in 10nmol/L paclitaxel group and control group for 24 h.Results Compared with control group, the expression levels of β-catenin protein in paclitaxel groups were decreased, the expression levels of β-catenin protein were significantly reduced when paclitaxel concentration at10 nmol/L(P<0.05). Compared with control group,the expression levels of p53 mRNA were up-regulated and c-jun mRNA were down-regulated in10nmol/L paclitaxel group(P <0.05). Conclusions Paclitaxel may Down-regulate the expression of β-catenin and up-regulate the p53 mRNA, then block the wnt/β-catenin signaling pathway and down-regulate c-jun mRNA in cholangiocarcinoma cell line QBC939.
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Key words:
- Paclitaxel /
- QBC939 /
- β-catenin /
- P53 /
- C-jun
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[1] [1]ROWINSKY E K,ONETTO N,CANETTA R M,et al.Taxol:the first of the taxanes,an important new class of antitumor agents[J].Semin Oncol,1992,19(6):646-662. [2] [2]YAMASAKI M,MURAKAMI I,NAKANO K,et al.Carboplatin plus weekly paclitaxel combined with bevacizumab as first-line treatment for non-small cell Lung cancer[J].Anticancer Res,2017,37(2):923-928. [3] [3]KANG F C,CHEN P J,PAN B S,et al.Apoptotic effect of cordycepin combined with cisplatin and/or paclitaxel on MA-10 mouse Leydig tumor cells[J].Onco Targets Ther,2015,8(1):2345-2360. [4] [4]CADAMURO M,SPAGNUOLO G,SAMBADO L,et al.Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma[J].Cancer Res,2016,76(16):4775-4784. [5] [5]KIM S W,HASANUZZAMAN M,CHO M,et al.Role of14-3-3 sigma in over-expression of P-gp by rifampin and paclitaxel stimulation through interaction with PXR[J].Cell Signal,2017,2(31):124-134. [6] [6]ITO Y,KIKUCHI E,TANAKA N,et al.Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer[J].BMC Cancer,2015,4(29):324. [7] [7]DZIADYK J M,SUI M,ZHU X,et al.Paclitaxel-induced apoptosis may occur without a prior G2/M-phase arrest[J].Anticancer Res,2004,24(1):27-36. [8] [8]LI S,YANG L,WANG J,et al.Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells[J].Oncotarget,2016,7(35):57145-57159. [9] [9]YING L,ZHU Z,XU Z,et al.Cancer associated fibroblast-derived hepatocyte growth factor inhibits the paclitaxel-Induced apoptosis of lung cancer A549 cells by up-regulating the PI3K/Akt and GRP78 signaling on a microfluidic platform[J].PLo S One,2015,10(6):e0129593. [10] [10]ZHANG C,ZHANG Z,ZHANG S,et al.Targeting of Wnt/β-catenin by anthelmintic drug pyrvinium enhances sensitivity of ovarian cancer cells to chemotherapy[J].Med Sci Monit,2017,23(16):266-275. [11] [11]SHEN D Y,ZHANG W,ZENG X,et al.Inhibition of Wnt/β-catenin signaling downregulates P-glycoprotein and reverses multi-drug resistance of cholangiocarcinoma[J].Cancer Sci,2013,104(10):1303-1308. [12] [12]AHRENDT S A,RASHID A,CHOW J T,et al.p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer[J].J Hepatobiliary Pancreat Surg,2000,7(4):426-431. [13] [14]SUTO T,HABANO W,SUGAI T,et al.Aberrations of the K-ras,p53,and APC genes in extrahepatic bile duct cancer[J].J Surg Oncol,2000,73(3):158-163. [14] [15]KHAN S A,THOMAS H C,TOLEDANO M B,et al.p53Mutations in human cholangiocarcinoma:a review[J].Liver Int,2005,25(4):704-716. [16]周彦明,朱有全,冯颖.癌基因c-Fos、c-Jun在胆系恶性肿瘤中的表达[J].中华普通外科杂志,2002,17(2):123.
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