Abstract:【Objective】 To study the effects of ghrelin on the expression of breast cancer resistance protein(BCRP) in breast cancer cell line. 【Methods】Human breast cancer cell line MDA-MB-231 were cultured and treated with ghrelin, doxorubicin, and ghrelin combined with doxorubicin. The tunnel method was used to detect cell apoptosis. The Western-blot method was used to detect p-P38, P38, and BCRP protein levels. 【Results】Tunnel assay showed that under the addition of ghrelin, the human breast cancer cell MDA-MB-231 proliferated and the apoptosis rate was significantly lower than when doxorubicin was used. Ghrelin combined with doxorubicin inhibits the killing effect of doxorubicin on the human breast cancer cell line MDA-MB-231(P<0.001). The P38 and p-P38 protein levels increased in the Ghrelin Group, and the protein expression of BCRP increased significantly as well. The P38 and p-P38 protein levels and BCRP protein expression decreased in the Ghrelin combined with doxorubicin group, but the decrease was less compared to the doxorubicin group (P<0.05). 【Conclusion】The P38MAPK signaling pathway activated by ghrelin promotes breast cancer cell BCRP expression, inhibiting the killing effects of doxorubicin-induced apoptosis of breast cancer cells.
曲文志;李子豪;张云微;金光华;杨蕾;涂巍. 生长激素释放肽对乳腺癌耐药蛋白表达的影响及意义[J]. 医学临床研究, 2016, 33(10): 1880-1882.
QU Wen-Zhi, LI Zi-Hao, ZHANG Yun-Wei,et al. Effect of Ghrelin on the Expression of Breast Cancer Resistance Protein (BCRP) in Breast Cancer Cells. JOURNAL OF CLINICAL RESEARCH, 2016, 33(10): 1880-1882.
[1] Acconcia F. Ubiquitin in traffiking: the network at work[J].Exp Cell Res,2009, 315(9): 1610-1618. [2] Zhou Y. Effect of the novel antipsychotic drug perospironeon P-glycoprotein function and expression in Caco-2 cells [J].Eur J Clin Pharmacol,2008, 64(7): 697-703. [3] Sato TNY, Shiimura Y, Ohgusu H,et al.Structure, regulation and function of ghrelin[J].J Biochem,2012 ,151(2):119-128. [4] Lu XZX, Feng J, Liou AP, et al. Postprandial inhibition of gastric ghrelin secretionby long-chain fatty acid through GPR120 in isolated gastricghrelin cells and mice[J].Am J Physiol Gastrointest Liver Physiol,2012,303(3):367-376. [5] NanzerAM, Khalaf S, Mozid AM, et al. Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway[J].Eur J Endocrinol,2004,151(2):223-240. [6] Mazzocchi G, Neri G, Rucinski M, et al. Ghrelin enhances the growth of cultured human adrenal zona glomerulosa cells by exerting MAPK-mediated proliferogenic and antiapoptotic effects[J].Peptides,2004,25(8):1269-1277. [7] Hsiao PW, Chang CC, L iu HF, et al. Activation of p38m itogen - activated protein kinase by celecoxib oppositely regulates surviv in and gamm a- H 2AX in human colorectal cancer cells[J].Toxicol Appl Pharmacol,2007, 222( 1 ): 97-104. [8] Lin JC, Chang SY, Hsieh DS,et al.Modulation of mitogen-activated protein kinase cascades by differentiation-1 protein: acquired drug resistance of hormone independent prostate cancer cells[J].J Urol,2005,174(5): 2022. [9] Pan YY, Xu SP, Wei W. Effect of combined nimesulide and adriamycin on proliferation and apoptosis in hepatocellular carcinoma cell line HepG2[J].Chin Pharmacol Bull,2006, 22( 7 ) :884-887. [10] Jeffery PL, Murray RE, Yeh AH,et al.Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines[J].Endocr Relat Cancer,2005,12(4): 839-850. [11] Meyer ZU,Schwabedissen HE,Grube M,et al. Epidermal growth factor-mediated activation of the map kinase cascade results in altered expression and function of ABCG2(BRCP)[J].Durg Metab Dispos,2006,34(4):524-533. [12] 焦今文,王蕾,温放,等.p38MAPK在不同化疗后卵巢癌中的表达及临床意义[J].中国现代医学杂志,2011,21(15):1828. [13] Wang X , Wang XL , Chen HL,et al. Ghrelin inhibits doxorubicin cardiotoxicity by inhibiting excessive autophagy through AMPK and p38-MAPK[J].Biochem Pharmacol,2014,88(3):334-350. [14] 曾少波,兰明银,菅志远,等. 乳腺癌细胞耐药过程中 p38MAPK活性与细胞凋亡的关系[J].中华乳腺病杂志:电子版,2009,3(1):46-52.