Delphinidin sensitizes anti-tumor effect to HER-2+breast cancer cells by combining with 3-MA
-
摘要: 目的:研究飞燕草素（delphinidin,Dp）联合自噬抑制剂3-甲基腺嘌呤（3-Methyladnine,3-MA）对HER-2+乳腺癌细胞MDA-MB-453的抑制效应。方法:用不同浓度飞燕草素处理MDA-MB-453细胞,CCK-8检测细胞增殖情况;荧光斑点实验和Weston Blot实验检测飞燕草素对细胞自噬的诱导情况;Weston Blot实验检测3-MA对自噬的抑制状况,CCK-8检测飞燕草素联合3-MA对细胞增殖状况的影响。结果:飞燕草素能有效抑制MDA-MB-453细胞增殖,诱导MDA-MB-453细胞自噬并呈剂量依赖效应;3-MA有效抑制MDA-MB-453细胞自噬,同时增强自噬飞燕草素抗HER-2+乳腺癌细胞MDA-MB-453增殖效应。结论:飞燕草素联合自噬抑制剂3-MA,能促进飞燕草素抗HER-2+乳腺癌细胞MDA-MB-453增殖。Abstract: Objective: To research the effect of delphinidin( Dp) combines with 3- Methyladnine( 3- MA),inhibitor of autophagy,to HER( human epidermal growth factor receptor-2,HER-2) positive breast cancer cell MDA- MB-453.Methods:HER-2+breast cancer cells MDA- MB-453 were treated by Dp.Proliferation of MDA- MB-453 cells was detected by CCK-8.Fluorescence dot assay and Weston Blot were used to identify autophagy in breast cancer cells. Weston blot was used to assay condition of autophagy inhibition of 3- MA to MDA- MB- 453 cell and CCK- 8 tests combination effect of Dp and 3- MA to MDA- MB-453 cell.Results: Dp suppressed proliferation effectively and induced autophagy in dose- dependent manner in MDA- MB-453 cells.However,3- MA could restrain the autophagy,which sensitized anti- proliferation of Dp to MDA- MB- 453 cell.Conclusion: Combination of Dp and 3- MA which suppresses autophagy can sensitize anti- proliferation effect of HER-2+breast cancer cell MDA- MB-453.
-
Keywords:
- delphinidin /
- breast cancer /
- autophagy /
- sensibilization
-
[1] Ferlay J,Soerjomataram I,Ervik M,et al.GLOBOCAN 2012v1.0,Cancer Incidence and Mortality Worldwide:IARC Cancer Base No.11.Lyon,France:International Agency for Research on Cancer;2013.Available from:http://globocan.iarc.fr.Accessed on 28 May 2014.
[2] Slamon DJ,Leyland-Jones B,Shak S,et al.Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2[J].N Engl J Med,2001,344:783-792.
[3] Guo S,Wong S.Cardiovascular toxicities from systemic breast cancer therapy[J].Front Oncol,2014(4):346.
[4] Duchnowska R,Biernat W,Szostakiewicz B,et al.Correlation between Quantitative HER-2 protein expression and risk for brain metastases in HER-2+advanced breast cancer patients receiving Trastuzumab-containing therapy[J].Oncologist,2012,17:26-35.
[5] Pratheeshkumar P,Son YO,Korangath P,et al.Phytochemicals in cancer prevention and therapy[J].Biomed Res Int,2015:324021.
[6] Chen XY,Zhou J,Luo LP,et al.Black rice anthocyanins suppress metasis of breast cancer cells by targeting RAS/RAF/MAPK pathway[J].Biomed Res Int,2015:414250.
[7] 罗丽萍,余小平,韩彬,等.花青素主要成分与HER-2激酶区的分子对接[J].生物工程学报,2014,30(3):504-513. [8] Lu J,Sun DP,Gao S,et al.Cyclovirobuxine D induces autophagy-associated cell death via the Akt/m TOR Pathway in MCF-7 human breast cancer cells[J].J Pharmacol Sci,2014,125(1):74-82.
[9] Shi YM,Yang L,Geng YD,et al.Polyphyllin I inducedapoptosis is enhanced by inhibition of autophagy in human hepatocellular carcinoma cells[J].Phytomedicine,2015,22(13):1139-1149.
[10] Rodríguez CE,Reidel SI,Bal de Kier JofféED,et al.Autophagy protects from trastuzumab-induced cytotoxicity in HER2 overexpressing breast tumor spheroids[J].PLo S One,2015,10(9):e0137920.
[11] Brigger D,Schlfli AM,Garattini E,et al.Activation of RARαinduces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity[J].Cell Death Dis,2015(6):e1861.
[12] Ko H,Jeong MH,Jeon H,et al.Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis,by inducing DR5 and causing caspase-mediated HDAC3 cleavage[J].Oncotarget,2015,6(12):9970-9984.
[13] Lim W,Jeong W,Song G.Delphinidin suppresses proliferation and migration of human ovarian clear cell carcinoma cells through blocking AKT and ERK1/2 MAPK signaling pathways[J].Mol Cell Endocrinol,2016,15(422):172-181.
[14] Chakrabarti M,Ray SK.Direct transfection of miR-137mimics is more effective than DNA demethylation of miR-137promoter to augment anti-tumor mechanisms of delphinidin in human glioblastoma U87MG and LN18 cells[J].Gene,2015,573(1):141-152.
[15] Keravis T,Favot L,Abusnina AA,et al.Delphinidin Inhibits Tumor Growth by Acting on VEGF Signalling in Endothelial Cells[J].PLo S One,2015,10(12):e0145291.
[16] Wu YT,Tan HL,Shui G,et al.Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase[J].J Biol Chem,2010,285(14):10850-10861.
[17] Levine B,Kroemer G.Autophagy in the pathogenesis of disease[J].Cell,2008,132(1):27-42.
[18] Chen WC,Hsu KY,Hung CM,et al.The anti-tumor efficiency of pterostilbene is promoted with a combined treatment of Fas signaling or autophagy inhibitors in triple negative breast cancer cells[J].Food Funct,2014,5(8):1856-1865.
[19] Yan-Cong Li,Shu-Ming He,Zhi-Xu He,et al.Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/m TOR pathway in human non-small cell lung cancer cells[J].Cancer Lett,2014,344(2):239-259.
[20] Ambjrn M,Ejlerskov P,Liu Y,et al.IFNB1/interferon-β-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function[J].Autophagy,2013,9(3):287-302.
[21] Amaral C,Varela C,Azevedo M,et al.Effects of steroidal aromatase inhibitors on sensitive and resistant breast cancer cells:aromataseinhibition and autophagy[J].J Steroid Biochem Mol Biol,2013,135:51-59.
[22] Lozy F,Cai-McRae X,Teplova I,et al.ERBB2overexpression suppresses stress-induced autophagy and renders ERBB2-induced mammary tumorigenesis independent of monoallelic<i>Becn1</i>loss[J].Autophagy,2014,30,10(4):662-676.
计量
- 文章访问数:
- HTML全文浏览量:
- PDF下载量:
下载:
