The role of miR-21 in Endostar combined with X-ray irradiation of cardiac fibroblasts
Cao Dongdong1,2, Ouyang Weiwei1,2, Zhao Xing3, Su Shengfa1, Zhang Jun4, Fu Shimei1,2, Feng Zhangxin2, Li Qingsong2, Ma Zhu1, Yang Wengang2, Chen Xiaxia2, Lu Bing1,2
1Affiliated Hospital of Guizhou Medical University/Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China; 2Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang 550004, China; 3Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang 550004, China; 4Department of Pathology, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Abstract：Objective To investigate the implication of micro RNA-21(miR-21) in Endostar combined with X-ray irradiation of cardiac fibroblasts (CF). Methods Rat CFs were used in this experiment and been divided into the blank control group, 10Gy X-ray irradiation group, Endostar group, 10Gy X-ray+Endostar group, 10Gy X-ray+Endostar+NC mimic group (negative control 1), 10Gy X-ray+Endostar+miR-21 mimic group, 10Gy X-ray+Endostar+NC inhibitor group (negative control 2) and 10Gy X-ray+Endostar+miR-21 inhibitor group. The proliferation of CF was determined by Methyl thiazolyl tetrazolium (MTT) assay. The expression level of Collagen Ⅰ protein was analyzed by Western blot. The expression levels of Collagen Ⅰ and miR-21 mRNA were assayed by real-time quantitative polymerase chain reaction (q-PCR). Results In the 10Gy X-ray+Endostar+miR-21 mimic group, the CF proliferation, Collagen Ⅰ and miR-21 mRNA were increased significantly compared with those in the blank control group, 10Gy X-ray+Endostar group, and negative control group 1 (all P<0.05). In the 10Gy X-ray+Endostar+miR-21 inhibitor group, the CF proliferation and expression levels of Collagen Ⅰ mRNA were decreased significantly compared with those in the blank control group, 10Gy X-ray+Endostar group and negative control group 2(all P<0.05). Conclusions The CF proliferation and Collagen Ⅰ expression are increased when the expression level of miR-21 gene is simulated. When inhibiting the expression of miR-21 gene, the CF proliferation and Collagen Ⅰ expression are reduced.
Cao Dongdong,Ouyang Weiwei,Zhao Xing et al. The role of miR-21 in Endostar combined with X-ray irradiation of cardiac fibroblasts[J]. Chinese Journal of Radiation Oncology, 2022, 31(4): 370-375.
[1] Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action[J]. Exp Cell Res, 2006, 312(5):594-607. DOI:10.1016/j.yexcr.2005.11.015. [2] Jiang XD, Dai P, Wu J, et al. Effect of recombinant human endostatin on radiosensitivity in patients with non-small-cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2012, 83(4):1272-1277. DOI:10.1016/j.ijrobp.2011.09.050. [3] Zhong Z, Gu X, Zhang Z, et al. Recombinant human endostatin combined with definitive chemoradiotherapy as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma of the oesophagus[J]. Br J Radiol, 2012, 85(1019):e1104-e1109. DOI:10.1259/bjr/15321801. [4] Ke QH, Zhou SQ, Huang M, et al. Early efficacy of endostar combined with chemoradiotherapy for advanced cervical cancers[J]. Asian Pac J Cancer Prev, 2012, 13(3):923-926. DOI:10.7314/APJCP.2012.13.3.923. [5] Jing Q, Xinyu Q, Rougcheng L. Recombinant human endostatin-associated acute left heart failure[J]. Clin Oncol (R Coll Radiol), 2008, 20(3):268. DOI:10.1016/j.clon.2008.01.001. [6] 万艳,欧阳伟炜,苏胜发,等. 放射联合重组人血管内皮抑制素致心肌纤维化的作用机制[J]. 中华放射肿瘤学杂志, 2020,29(4):294-299. DOI:10.3760/cma.j.cn113030-20190911-00009. Wan Y, Ouyang WW, Su SF, et al. Mechanism of radiation combined with recombinant human endostatin in inducing myocardial fibrosis[J]. Chin J Radiat Oncol,2020, 29(4):294-299. DOI:10.3760/cma.j.cn113030-20190911-00009. [7] Darby SC, Cutter DJ, Boerma M, et al. Radiation-related heart disease:current knowledge and future prospects[J]. Int J Radiat Oncol Biol Phys,2010, 76(3):656-665. DOI:10.1016/j.ijrobp.2009.09.064. [8] LaFramboise WA, Scalise D, Stoodley P, et al. Cardiac fibroblasts influence cardiomyocyte phenotype in vitro[J]. Am J Physiol Cell Physiol, 2007, 292(5):C1799-C1808. DOI:10.1152/ajpcell.00166.2006. [9] Pluteanu F, Nikonova Y, Holzapfel A, et al. Progressive impairment of atrial myocyte function during left ventricular hypertrophy and heart failure[J]. J Mol Cell Cardiol, 2018, 114:253-263. DOI:10.1016/j.yjmcc.2017.11.020. [10] Zeisberg EM, Kalluri R. Origins of cardiac fibroblasts[J]. Circulat Res, 2010, 107(11):1304-1312. DOI:10.1161/CIRCRESAHA.110.231910. [11] Roy S, Khanna S, Hussain SR, et al. MicroRNA expression in response to murine myocardial infarction:miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tens in homologue[J]. Cardiovasc Res, 2009, 82(1):21-29. DOI:10.1093/cvr/cvp015. [12] Villar AV, García R, Merino D, et al. Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients[J]. Int J Cardiol, 2013, 167(6):2875-2881. DOI:10.1016/j.ijcard.2012.07.021. [13] Adam O, Löhfelm B, Thum T, et al. Role of miR-21 in the pathogenesis of atrial fibrosis[J]. Basic Res Cardiol, 2012, 107(5):278. DOI:10.1007/s00395-012-0278-0. [14] Liang H, Zhang C, Ban T, et al. A novel reciprocal loop between microRNA-21 and TGF-βR Ⅲ is involved in cardiac fibrosis[J]. Int J Biochem Cell Biol, 2012, 44(12):2152-2160. DOI:10.1016/j.biocel.2012.08.019. [15] Karolina DS, Armugam A, Tavintharan S, et al. MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2diabetes mellitus[J]. PLoS One, 2011, 6(8):e22839. DOI:10.1371/journal.pone.0022839. [16] Okada M, Oba Y, Yamawaki H. Endostatin stimulates proliferation and migration of adult rat cardiac fibroblasts through PI3K/Akt pathway[J]. Eur J Pharmacol, 2015, 750:20-26. DOI:10.1016/j.ejphar.2015.01.019. [17] Sugiyama A, Hirano Y, Okada M, et al. Endostatin stimulates proliferation and migration of myofibroblasts isolated from myocardial infarction model rats[J]. Int J Mol Sci, 2018,19(3):e741. DOI:10.3390/ijms19030741. [18] Yamaguchi Y, Takihara T, Chambers RA, et al. A peptide derived from endostatin ameliorates organ fibrosis[J]. Sci Transl Med, 2012, 4(136):136ra71. DOI:10.1126/scitranslmed.3003421. [19] 覃晶,钱新宇,李爱民,等. 重组人血管内皮抑素心脏毒性作用的靶标及作用机制研究[J]. 药物不良反应杂志,2013, 15(6):336-341. DOI:10.3760/cma.j.issn.1008-5734.2013.06.010. Qin J, Qian XY, Li AM, et al. Target and mechanism of cardiotoxicity of recombinant human endostatin[J]. ADRJ, 2013,15(6):336-341. DOI:10.3760/cma.j.issn.1008-5734.2013.06.010. [20] 夏荣耀,张冉冉,陈复辉. 重组人血管内皮抑素对肺腺癌A549细胞生长及凋亡的影响[J]. 现代肿瘤医学,2014, 22(7):1511-1514. DOI:10.3969/j.issn.1672-4992.2014.07.09. Xia RY, Zhang RR, Cheng FH. Effect of endostar on the growth and apoptosis of lung cancer A549 cells[J]. Mod Oncol, 2014, 22(7):1511-1514. DOI:10.3969/j.issn.1672-4992.2014.07.09. [21] Ling Y, Lu N, Gao Y, et al. Endostar induces apoptotic effects in HUVECs through activation of caspase-3 and decrease of Bcl-2[J]. Anticancer Res, 2009, 29(1):411-417. [22] You ZY, Zhao Y, Liu F, et al. The radiosensitization effects of Endostar on human lung squamous cancer cells H-520[J]. Cancer Cell Int, 2010, 10:17. DOI:10.1186/1475-2867-10-17. [23] 许成云,倪庆桂,樊馨,等. 重组人血管内皮抑制素对肺微血管内皮细胞增殖及其周期分布的影响[J]. 临床肿瘤学杂志, 2009, 14(5):410-413. DOI:10.3969/j.issn.1009-0460.2009.05.006. Xu CY, Ni QG, Fan X, et al. Effect of endostar on proliferation and cell cycle of lung cancer microvasculature endothelial cell HPMEC[J]. Chin Clin Oncol, 2009, 14(5):410-413. DOI:10.3969/j.issn.1009-0460.2009.05.006. [24] Hanai J, Dhanabal M, Karumanchi SA, et al. Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1[J]. J Biol Chem, 2002, 277(19):16464-16469. DOI:10.1074/jbc.M112274200. [25] Yeh ET, Tong AT, Lenihan DJ, et al. Cardiovascular complications of cancer therapy:diagnosis, pathogenesis, and management[J]. Circulation, 2004, 109(25):3122-3131. DOI:10.1161/01.CIR.0000133187.74800.B9.
2022, Vol. 31 
