追毒方逆转三阴性乳腺癌MDA-MB-231细胞耐药的作用机制
Reverse Effect and Mechanism of Effective Components of Zhuidu Fang on Triple Negative Breast Cancer MDA-MB-231 Drug-Resistant Cells
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摘要: 目的 基于糖基转移酶β3GnT8探讨追毒方逆转三阴性乳腺癌MDA-MB-231细胞耐药的作用机制。方法 通过MTT法观察追毒方对MDA-MB-231耐药细胞增殖的抑制作用，通过转染β3GnT8得到高表达β3GnT8的MDA-MB-231/TAX细胞株，采用Western blot观察糖基转移酶β3GnT8和耐药蛋白BCRP、P-gp的表达，通过凝集素流式细胞术观察转染β3GnT8 MDA-MB-231/TAX细胞膜表面β3GnT8的荧光强度。结果 追毒方有效成分能明显抑制三阴性乳腺癌MDA-MB-231耐药细胞的增殖，作用72 h抑制率达到50.16%，能有效下调β3GnT8和耐药蛋白BCRP、P-gp的表达，并且β3GnT8的表达与BCRP、P-gp呈正相关。结论 追毒方可通过下调糖基转移酶β3GnT8，从而降低耐药蛋白BCRP、P-gp的表达，逆转三阴性乳腺癌MDA-MB-231细胞耐药性。
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关键词:
- 追毒方 /
- 三阴性乳腺癌MDA-MB-231耐药细胞 /
- β3GnT8 /
- 逆转耐药
Abstract: OBJECTIVE Based on glycosyltransferase β3GnT8， to investigate the mechanism of reverse effect on triple negative breast cancer MDA-MB-231 drug-resistance cells by Zhuidu Fang. METHODS The inhibition of MDA-MB-31 drug-resistance cells proliferation by Zhuidu Fang was detected by MTT assay. By interference and transfection of β3GnT8， high and low expressed β3GnT8 MDA-MB-231/TAX cell lines were obtained. Western blot was used to detect the protein expression of β3GnT8， and drug resistance protein BCRP and P-gp. Lectin flow cytometry was used to detect β3GnT8 fluorescence intensity on β3GnT8 transfected MDA-MB-231/TAX cells. RESULTS Zhuidu Fang effectively inhibited the proliferation of MDA-MB-231/TAX cells， and the inhibitory rate was 50.16% after 72 h. Zhuidu Fang significantly downregulated the protein expression of β3GnT8， BCRP and P-gp. The protein expression of β3GnT8 showed a positive correlation with BCRP and P-gp. CONCLUSION Zhuidu Fang can reverse the drug-resistance of MDA-MB-231 cell lines， which is associated with the downregulation of the expression of β3GnT8， BCRP and P-gp. -
[1] OSSOVSKAYA V， WANG Y， BUDOFF A， et al. Exploring molecular pathways of triple-negative breast cancer[J]. Genes Cancer， 2011， 2(9):870-879. [2] 王晓稼.2015年美国ASCO年会三阴性乳腺癌研究进展[J].中国肿瘤外科杂志， 2015， 7(3):141-145. [3] 刘敏，王明武.解毒破瘀法抑制三阴性乳腺癌复发与转移的临床研究[J].南京中医药大学学报，2016，32(2):111-113. [4] LIU CL， QIU H， LIN DD， et al. c-Jun-dependent β3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering N-glycan patterns[J]. Oncotarget， 2018(1):1-13. [5] QIU H， XU X， LIU M， et al. RNA interference mediated silencing of ppGalNAc T1 and ppGalNAc T2 inhibits invasion and increases chemosensitivitypotentially by reducing terminal α2，3 sialylation and MMP14 expression in triple negative breast cancer cells[J].Mol Med Rep，2017(15):3724-3734. [6] WANG Y， LU JJ， HE L， et al. Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II)[J]. PLoS ONE， 2011， 6:e23993. [7] PAN L， CHAI H， KINGHORN AD. The continuing search for antitumor agents from higher plants[J]. Phytochem Lett， 2010， 3（1）:1-8. [8] CAREY N， LA THANGUE NB. Histone deacetylase inhibitors: gathering pace[J]. Curr Opin Pharmacol， 2006， 6（4）:369-375. [9] GUO JM， CHEN HL， Wang GM， et al. Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-12 in gastric and colonic cancer cell lines and in human colorectal cancer[J]. Oncology， 2004， 67:271-276. [10] HUANG C， ZHOU J， WU S， et al. Cloning and tissue distribution of the human B3GALT7 gene， a member of the beta1，3-Glycosyltransferase family[J]. Glycoconj J， 2004，21:267-273. [11] LIU CL， QIU H， YU MY， et al. c-Jun-mediated β-1，3-N-acetylglucosaminyltransferase 8 expression: A novel mechanism regulating the invasion and metastasis of colorectal carcinoma cells[J].Oncol Lett，2017，14: 3722-3728. [12] 刘敏.中药解毒成分复方对乳腺癌作用和机理的实验研究[D]. 南京：南京中医药大学，2014. -
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