miR-377-5p通过抑制AKT1/GSK-3β通路增强食管癌细胞TE-1的放射敏感性

doi:10.3760/cma.j.cn113030-20190905-00362

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Abstract Objective To investigate the effect and mechanism of miR-377-5p on the radiosensitivity of esophageal cancer cell line TE-1. Methods Esophageal cancer cell line TE-1 was transfected with miR-377-5p mimic and miR-377-5p mimic NC to construct the TE-1 cells overexpressing miR-377-5p. After the transfected TE-1 cells were exposed to ionizing radiation, radiobiological parameters(D0,Dq,SF2) were detected by plate colony formation assay. Cell invasion ability was assessed by Transwell chamber assay, Cell migration ability was evaluated by cell scratch assay, Cell viability was assessed by CCK8 assay. Cell apoptosis and cell cycle were detected by flow cytometry, Western blot. The phosphorylation levels of AKT1 and GSK-3βwere measured by Western blot. Results At the doses of 2, 4, 6, and 8 Gy, the colony formation rate in each group was significantly decreased (all P<0.05), and the colony formation rate at the same irradiation dose in the miR-377-5p mimic group was significantly lower than that in the miR-377-5p mimic NC group (P<0.05). Compared with the miR-377-5pmimic NC group, the D0, Dq and SF2 at 2Gy were decreased significantly in the miR-377-5pmimic group (all P<0.05), and the radiosensitization ratio(D0 ratio) was 1.34. After 0 Gy ionizing radiation, the invasion, migration and proliferation abilities of TE-1 cells were significantly decreased, the level of cell apoptosis was significantly increased, the cell cycle was arrested in G1 phase, and the phosphorylation levels of AKT1 and GSK-3β were significantly decreased in the miR-377-5pmimic group (all P<0.05). Following 4 Gy irradiation, cell invasion, migration, proliferation abilities were decreased, the level of cell apoptosis was increased significantly, the G1 phase was significantly extended and the phosphorylation levels of AKT1 and GSK-3β were also decreased significantly in the miR-377-5pmimic group (all P<0.001). Conclusion miR-377-5p can increase the radiosensitivity of esophageal cancer cell line TE-1, which may be due to the inhibition of the AKT1/GSK-3β signaling pathway.

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	Ba Yuntao
	Wang Quan

Key words： miR-377-5p gene AKT1/GSK-3&beta signaling pathway Radiosensitivity

Received: 05 September 2019

Cite this article:

Ba Yuntao,Wang Quan. miR-377-5p enhances radiosensitivity of esophageal cancer cell line TE-1 by inhibiting AKT1/GSK-3β signaling pathway[J]. Chinese Journal of Radiation Oncology, 2020, 29(12): 1096-1101.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.cn113030-20190905-00362 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2020/V29/I12/1096

[1] 武二伟, 齐洪志, 赵化荣,等. 167例中晚期食管癌放化疗的疗效及预后[J]. 现代肿瘤医学, 2017, 25(3):385-389. DOI:10.3969/j.issn.1672-4992.2017.03.013.
Wu EW, Qi HZ, Zhao HR, et al. The efficacy and prognosis of radiotherapy and chemotherapy in 167 patients with advanced esophageal cancer[J]. Mode Oncol Med, 2017, 25(3):385-389. DOI:10.3969/j.issn.1672-4992.2017.03.013.
[2] 郭信伟. 治疗前血液炎性标志物对食管鳞癌患者放化疗疗效及预后的影响[J]. 中华放射医学与防护杂志, 2019, 39(3):202-207. DOI:10.3760/cma.j.issn.0254-5098.2019.03.008.Guo XW. Effect of blood inflammatory markers on the efficacy and prognosis of patients with esophageal squamous cell carcinoma before treatment[J]. Chin J Radiol Med Protect, 2019, 39(3):202-207. DOI:10.3760/cma.j.issn.0254-5098.2019.03.008.
[3] 郭信伟, 冀胜军, 周绍兵, 等. 胸段食管鳞状细胞癌术后淋巴结转移瘤大小对放化疗效果及预后的影响[J]. 国际肿瘤学杂志, 2018, 45(3):148-152. DOI:10.3760/cma.j.issn.1673-422X.2018.03.005.
Guo XW, Ji SJ, Zhou SB, et al. The effect of postoperative lymph node metastasis size on chemoradiotherapy and prognosis of thoracic esophageal squamous cell carcinoma[J]. Int J Oncol, 2018, 45(3):148-152. DOI:10.3760/cma.j.issn.1673-422X.2018.03.005.
[4] Liu H, Ren G, Zhu L, et al. The upregulation of miRNA-146a inhibited biological behaviors of ESCC through inhibition of IRS2[J]. Tumor Biol, 2016, 37(4):4641-4647. DOI:10.1007/s13277-015-4274-5.
[5] 贾亚旭,王成,张春妮. 血清miR-193a-3p,miR-337-5p和miR-483-5p在食管鳞状细胞癌诊断和预后中的应用[J]. 现代检验医学杂志, 2017, 32(2):5-9. DOI:10.3969/j.issn.1671-7414.2017.02.002.
Jia YX, Wang C, Zhang CN. Application of serum miR-193a-3p, miR-337-5p and miR-483-5p in diagnosis and prognosis of esophageal squamous cell carcinoma[J]. J Mode Labor Med, 2017, 32(2):5-9. DOI:10.3969/j.issn.1671-7414.2017.02.002.
[6] Su H, Hu N, Yang HH, et al. Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes[J]. Clin Canc Res, 2011, 17(9):2955-2966. DOI:10.1158/1078-0432. CCR-10-2724.
[7] Hui B, Chen X, Hui L, et al. Serum miRNA expression in patients with esophageal squamous cell carcinoma[J]. Oncol Lett, 2015, 10(5):3008-3013. DOI:10.3892/ol.2015.3642.
[8] Chaudhry MA. Radiation-induced microRNA:discovery, functional analysis, and cancer radiotherapy[J]. J Cell Biochem, 2014, 115(3):436-449. DOI:10.1002/jcb.24694.
[9] Korpela E, Vesprini D, Liu SK. MicroRNA in radiotherapy:miRage or miRador?[J]. Br J Cancer, 2015, 112(5):777-782. DOI:10.1038/bjc.2015.6.
[10] Li AL, Chung TS, Chan YN, et al. microRNA expression pattern as an ancillary prognostic signature for radiotherapy[J]. J Transl Med, 2018, 16(1):341-355. DOI:10.1186/s12967-018-1711-4.
[11] 胡格, 朱宇, 周月鹏,等. 白藜芦醇联合放疗对食管癌细胞株凋亡的影响[J]. 江苏大学学报(医学版), 2017, 27(3):194-199. DOI:10.13312/j.issn.1671-7783.y170019.
Hu G, Zhu Y, Zhou YP, et al. Effect of resveratrol combined with radiotherapy on apoptosis of esophageal cancer cell lines[J]. J Jiangsu Univ (Med ed), 2017, 27(3):194-199. DOI:10.13312/j.issn.1671-7783.y170019.
[12] 喻隼锋, 程洁, 耿爽, 等. 辛伐他汀对肺癌细胞株Lewis增殖侵袭能力及放疗增敏的影响[J]. 中华肿瘤杂志, 2017, 39(4):245-249. DOI:10.3760/cma.j.issn.0253-3766.2017.04.002.
Yu SF, Cheng J, Geng S, et al. Effects of simvastatin on proliferation, invasion and radiosensitivity of lung cancer cell line Lewis[J]. Chin J Oncol, 2017, 39(4):245-249. DOI:10.3760/cma.j.issn.0253-3766.2017.04.002.
[13] 陈苗, 沈帅, 于承仟,等. MicroRNA-34a对多种肿瘤细胞迁移的影响及其作用机制探讨[J]. 现代肿瘤医学, 2017, 25(1):140-143. DOI:10.3969/j.issn.1672-4992.2017.01.037.
Chen M, Shen S, Yu CQ, et al. Effects of microRNA-34a on the migration of a variety of tumor cells and its mechanism[J]. Mode Canc Med, 2017, 25(1):140-143. DOI:10.3969/j.issn.1672-4992.2017.01.037.
[14] 刘浩, 马俊, 李涛. 长链非编码RNA HOTAIR参与肿瘤转移的研究进展[J]. 海南医学, 2018, 29(8):1133-1135. DOI:CNKI:SUN:HAIN.0.2018-08-028.
Liu H, Ma J, Li T. Research progress of long non coding RNA HOTAIR in tumor metastasis[J]. Hainan Med Sci, 2018, 29(8):1133-1135. DOI:CNKI:SUN:HAIN.0.2018-08-028.
[15] Shen Z, Xu L, Li J, et al. Capilliposide C sensitizes esophageal squamous carcinoma cells to oxaliplatin by inducing apoptosis through the pi3k/akt/mtor pathway[J]. Med Monit, 2017, 23:2096-2103. DOI:10.12659/MSM.901183.
[16] 金迎迎,包兴. 辛伐他汀通过调控PI3K/AKT通路介导的EMT参与放疗诱导的食管癌细胞耐受[J]. 西安交通大学学报(医学版), 2019, 40(1):40-45. DOI:10.7652/jdyxb201901006.
Jin YY, Bao X. Simvastatin participates in radiation-induced esophageal cancer cell tolerance through regulating PI3K/ Akt pathway mediated EMT[J]. J Xi'an Jiaotong Unive (Med ed), 2019, 40(1):40-45. DOI:10.7652/jdyxb201901006.
[17] 韦柳婷,冯洁,莫书荣. PI3K-Akt信号通路与肿瘤相关性的研究进展[J]. 肿瘤学杂志, 2014, 20(4):331-336. DOI:10.11735/j.issn.1671-170X.2014.04. B015.
Wei LT, Feng J, Mo SR. Research progress of PI3K Akt signaling pathway and tumor[J]. J Chin Oncol, 2014, 20(4):331-336. DOI:10.11735/j.issn.1671-170X.2014.04. B015.
[18] 郭扬,曲国蕃. GSK3β在恶性肿瘤中的作用及研究现状[J]. 现代生物医学进展, 2012, 12(22):4390-4392. DOI:CNKI:SUN:SWCX.0.2012-22-052.
Guo Y, Qu GF. The role and research status of GSK3 β in malignant tumor[J]. Prog Mode Biomed, 2012, 12(22):4390-4392. DOI:CNKI:SUN:SWCX.0.2012-22-052.
[19] Ong CS, Zhou J, Ong CN. Luteolin induces G1 arrest in human nasopharyngeal carcinoma cells via the Akt-GSK-3β-Cyclin D1 pathway[J]. Cancer Letters, 2010, 298(2):167-175. DOI:10.1016/j.canlet.2010.07.001.
[20] Zhu X, Wang S, Yu L, et al. TL-2 attenuates β-amyloid induced neuronal apoptosis through the AKT/GSK-3β/β-catenin pathway[J]. Int J Neuropsychopharmacol, 2014, 17(9):1511-1519. DOI:10.1017/S1461145714000315.