miRNA-34a在胃癌细胞KATOⅢ中对5-Fu的增敏作用
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摘要
目的研究miR-34a在胃癌细胞KATOⅢ中对5-氟尿嘧啶(5-Fu)化疗敏感性的影响。方法采用定量PCR检测人正常胃黏膜细胞GES-1、胃癌细胞株BGC823、KATOⅢ、MGC803、MKN 45及SGC7901,检测5例胃癌及癌旁正常组织中miRNA-34a的表达水平。选择恶性程度较高的KATOⅢ细胞进一步研究,通过miR-34amimics上调胃癌细胞KATOⅢ中miR-34a的表达,通过MTT法检测肿瘤细胞对不同浓度5-Fu耐药活性的变化,以及肿瘤细胞增殖能力的变化。结果胃癌细胞BGC823,KATOⅢ,MGC803,MKN 45及SGC7901中miRNA-34a处于相对低表达水平,miR-34a在5例胃癌组织中的表达低于癌旁正常组织。选取miR-34a低表达的KATOⅢ细胞株,通过miR-34amimics上调miR-34a的表达后,药物浓度反应曲线显示,与negative control(NC)组比较,miR-34amimics组IC_(50)值下降(P<0.05),肿瘤细胞的增殖能力被miR-34a抑制(P<0.05)。结论 miR-34a在胃癌细胞KATOⅢ中提高了5-Fu的药物敏感性,同时抑制胃癌细胞KATOⅢ的增殖能力。
Objective To explore the function of miRNA-34 aon chemosensitivity of 5-Fu in gastric cancer cell KATOⅢ.Methods The expression of miRNA-34 ain gastric cancer cell lines BGC823,KATOⅢ,MGC803,MKN 45 and SGC7901 were examined by real-time PCR.Also 5 gastric cancer tissues and adjacent normal tissues were selected from gastric cancer specimens and the expression of miR-34 awas examined by real-time PCR.The alteration of KATOⅢ cells resistance(IC_(50))to 5-Fu was detected by MTT after miR-34 awas up-regulated by miRNA mimics.Also the MTT was used to detect KATOⅢ cell proliferation after miR-34 aup-regulated by miRNA mimics.Results The miRNA-34 a was in low expression statue in BGC823,BGC823,KATOⅢ,MGC803,MKN 45 and SGC7901 cell lines(P<0.05).Compared with the adjacent normal tissue,miR-34 awas relatively low expressed in gastric cancer tissue(P<0.05).Compared with negative control,the IC_(50) of 5-Fu decreased in miR-34 amimics group in KATOⅢ cells,and cell proliferation was reduced in miR-34 amimics group(P<0.05).Conclusion Our findings suggested that miR-34 ainhibit gastric cancer cell KATOⅢ and induce chemo-sensitization in P53-deficient cell lines.
Objective To explore the function of miRNA-34 aon chemosensitivity of 5-Fu in gastric cancer cell KATOⅢ.Methods The expression of miRNA-34 ain gastric cancer cell lines BGC823,KATOⅢ,MGC803,MKN 45 and SGC7901 were examined by real-time PCR.Also 5 gastric cancer tissues and adjacent normal tissues were selected from gastric cancer specimens and the expression of miR-34 awas examined by real-time PCR.The alteration of KATOⅢ cells resistance(IC_(50))to 5-Fu was detected by MTT after miR-34 awas up-regulated by miRNA mimics.Also the MTT was used to detect KATOⅢ cell proliferation after miR-34 aup-regulated by miRNA mimics.Results The miRNA-34 a was in low expression statue in BGC823,BGC823,KATOⅢ,MGC803,MKN 45 and SGC7901 cell lines(P<0.05).Compared with the adjacent normal tissue,miR-34 awas relatively low expressed in gastric cancer tissue(P<0.05).Compared with negative control,the IC_(50) of 5-Fu decreased in miR-34 amimics group in KATOⅢ cells,and cell proliferation was reduced in miR-34 amimics group(P<0.05).Conclusion Our findings suggested that miR-34 ainhibit gastric cancer cell KATOⅢ and induce chemo-sensitization in P53-deficient cell lines.
引文
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[4]Pagliarini R,Shao W,Sellers W R.Oncogene addiction:pathways of therapeutic response,resistance,and road maps toward a cure[J].EMBO Rep,2015,16(3):280-296.
[5]Kovalev A A,Tsvetaeva D A,Grudinskaja T V.Role of ABC-cassette transporters(MDR1,MRP1,BCRP)in the development of primary and acquired multiple drug resistance in patients with early and metastatic breast cancer[J].Exp Oncol,2013,35(4):287-290.
[6]Wang Y,Wang X,Zhao H,et al.Clusterin confers resistance to TNF-alpha-induced apoptosis in breast cancer cells through NF-kappaB activation and Bcl-2overexpression[J].J Chemother,2012,24(6):348-357.
[7]Sandhu R,Roll J D,Rivenbark A G,et al.Dysregulation of the epigenome in human breast cancer:contributions of gene-specific DNA hypermethylation to breast cancer pathobiology and targeting the breast cancer methylome for improved therapy[J].Am J Pathol,2015,185(2):282-292.
[8]Cao W,Wei W,Zhan Z,et al.Regulation of drug resistance and metastasis of gastric cancer cells via the microRNA647-ANK2axis[J].Int J Mol Med,2018,41(4):1958-1966.
[9]Xu X,Yu S,Sun W,et al.MiRNA signature predicts the response of patients with advanced lung adenocarcinoma to platinum-based treatment[J].J Cancer Res Clin Oncol,2018,144(3):431-438.
[10]Zhang J,Qiu W,Xu S,et al.MicroRNA-625inhibits the proliferation and increases the chemosensitivity of glioma by directly targeting AKT2[J].Am J Cancer Res,2017,7(9):1835-1849.
[11]Lu C,Xie Z,Peng Q.MiRNA-107enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bclw in non small cell lung cancer[J].Am J Cancer Res,2017,7(9):1863-1873.
[12]Liu Y,Zhu S T,Wang X,et al.MiR-200cregulates tumor growth and chemosensitivity to cisplatin in osteosarcoma by targeting AKT2[J].Sci Rep,2017,7(1):13598.
[13]Xiao W,Lou N,Ruan H,et al.Mir-144-3p promotes cell proliferation,metastasis,sunitinib resistance in clear cell renal cell carcinoma by downregulating ARID1A[J].Cell Physiol Biochem,2017,43(6):2420-2433.
[14]Ge X,Cui H,Zhou Y,et al.miR-320a modulates cell growth and chemosensitivity via regulating ADAM10in gastric cancer[J].Mol Med Rep,2017,16(6):9664-9670.
[15]Wu G,Wang J,Chen G,et al.microRNA-204modulates chemosensitivity and apoptosis of prostate cancer cells by targeting zinc-finger E-box-binding homeobox 1(ZEB1)[J].Am J Transl Res,2017,9(8):3599-3610.
[16]Cheng M W,Shen Z T,Hu G Y,et al.Prognostic significance of microRNA-7and its Roles in the regulation of cisplatin resistance in lung adenocarcinoma[J].Cell Physiol Biochem,2017,42(2):660-672.
[17]Xiong Y,Sun F,Dong P,et al.iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3signaling[J].J Exp Clin Cancer Res,2017,36(1):48.
[18]Raychaudhuri M,BrongerH,Buchner T,et al.MicroRNAs miR-7and miR-340predict response to neoadjuvant chemotherapy in breast cancer[J].Breast Cancer Res Treat,2017,162(3):511-521.
[19]Hummel R,Hussey D J,Haier J.MicroRNAs:predictors and modifiers of chemo-and radiotherapy in different tumour types[J].Eur J Cancer,2010,46(2):298-311.
[20]Li H Y,Liang J L,Kuo Y L,et al.miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer[J].Breast Cancer Res,2017,19(1):133.
[21]Yu G,Jia B,Cheng Y,et al.MicroRNA-429sensitizes pancreatic cancer cells to gemcitabine through regulation of PDCD4[J].Am J Transl Res,2017,9(11):5048-5055.
[22]李璧辰,王洁,潘玉婷,等.细菌耐药性调查及与抗菌药物使用相关性分析[J].西北药学杂志,2017,32(5):666-670.
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[24]Li Y,Zhang J,Liu Y,et al.miR-30a-5p confers cisplatin resistance by regulating IGF1Rexpression in melanoma cells[J].BMC Cancer,2018,18(1):404.
[25]Feng Q,He P,Wang Y.microRNA-223-3p regulates cell chemo-sensitivity by targeting FOXO3in prostatic cancer[J].Gene,2018,658:152-158.
[26]Li Y,Liang Y,Sang Y,et al.miR-770supresses the chemo-resistance and metastasis of triple negative breast cancer via direct targeting of STMN1[J].Cell Death Dis,2018,9(1):14.