mTOR通路激活后上调SNCG表达水平抑制乳腺癌细胞辐射敏感性的研究

doi:10.3969/j.issn.1004-616x.2017.03.009

Abstract

Abstract: OBJECTIVE:To investigate the involvement of mTOR-regulated SNCG expression in the control of radiation sensitivity in T47D breast cancer cells. METHODS:Expression levels of tumor-related genes in T47D cells were investigated after their irradiation with different doses of γ-rays. Western blot analysis was performed to determine the level of SNCG expression with or without the treatments of phosphatidic acid (PA;an mTOR pathway activator),and with 4 Gy γ-rays with or without PA treatment. Furthermore,SNCG expression was inhibited by transfection with SNCG-siRNA,and colony formation assay was performed to document radiation sensitivity. RESULTS:After γ-rays irradiation,there was a remarkable up-regulation of mTOR expression in T47D cells. However,radiation sensitivity was altered in PA-treated cells,suggesting that mTOR pathway was involved in the regulation of radio-sensitivity in these cells. From the qPCR and Western blot analyses,SNCG expression was up-regulated in either γ-rays irradiated or PA-treated T47D cells,indicating that mTOR-mediated the expression of SNCG which reduced the radiation sensitivity in T47D cells. Furthermore,transfection of cells with SNCG-siRNA significantly suppressed colony formation,suggesting that knockdown of SNCG expression can improve radiation sensitivity in breast cancer cells. CONCLUSION:Our study show that mTOR mediated the expression of SNCG and the subsequent radiation sensitivity of breast cancer cells. Our data suggest that down-regulation of SNCG expression may increase the sensitivity of radiotherapy and this may be helpful for the treatment of the patients with breast cancer.

Key words: breast cancer, mTOR pathway, SNCG, irradiation therapy

CLC Number:

R811.5

WU Lina, GAO Gang, LIU Jianxiang. Activation of mTOR signaling pathway can reduce radiation sensitivity through up-regulating SNCG expression in breast cancer cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(3): 205-210,215.

References

[1] ZHAO Z Q,YU Z Y,OUYANG X N,et al. Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway[J]. Oncol Lett,2016,12(1):63-68.
[2] FAN Y X,DAI Y Z,WANG X L,et al. MiR-18a upregulation enhances autophagy in triple negative cancer cells via inhibiting mTOR signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2016,20(11):2194-2200.
[3] LIANG W,MIAO S,ZHANG B,et al. Synuclein γ protects Akt and mTOR and renders tumor resistance to Hsp90 disruption[J]. Oncogene,2015,34(18):2398-2405.
[4] 陈衍,韩晟,刘文超. PI3K/AKT/mTOR通路调控乳腺癌细胞FASN过表达的分子机制[J]. 现代肿瘤医学,2013,1(3):1-4.
[5] 郭婧昀,姚广裕,顾繁,等. 曲妥珠单抗对HER-2过表达乳腺癌细胞株mTOR信号通路影响的观察[J]. 中华肿瘤防治杂志,2012,13(17):983-986.
[6] 白玉盘,杨小利,欧周罗. mTOR信号通路介导产生XCL1可促进乳腺癌耐药细胞株的增殖[J]. 中国癌症杂志,2014, 10(25):770-776.
[7] 李明,周永,谭宗才,等. 三羟异黄酮对HER2/neu高表达人乳腺癌细胞辐射敏感性的影响[J]. 西南国防医药,2014, 4(21):358-361.
[8] 李明,马建新,王忠明,等. 槲皮素对乳腺癌MCF-7细胞电离辐射敏感性的影响[J]. 中国医药导报,2011,25(31):18-20.
[9] 李明,周永,谭宗才,等. 三羟异黄酮对HER2/neu高表达人乳腺癌细胞辐射敏感性的影响[J]. 西南国防医药,2014, 4(21):358-361.
[10] JI H,LIU YE,JIA T,et al. Identification of a breast cancer-specific gene,SNCG,by direct differential cDNA sequencing[J]. Cancer Res,1997,57(4):759-764.
[11] HE J,CHEN W,WU H,et al. Downregulation of SNCG may correlate with better outcome of neoadjuvant chemotherapy for triple-negative breast cancer[J]. Oncol Lett,2012,4(6):1209-1212.
[12] XIE J L,WANG X M,CHRISTOPHER G P. mTOR inhibitors in cancer therapy[J/OL]. F1000Res,2016,5:2078[2016-08-25]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007757/.DOI:1012688/f1000research.9207.1.
[13] DAVERI E,MAELLARO E,VALACCHI G,et al. Inhibi-tions of mTORC1 and 4EBP-1 are key events orchestrated by Rottlerin in SK-Mel-28 cell killing[J]. Cancer Lett,2016, 380(1):106-113.
[14] LIU ZG,TANG J,CHEN Z,et al. The novel mTORC1/2 dual inhibitor INK128 enhances radiosensitivity of breast cancer cell line MCF-7[J]. Int J Oncol,2016,49(3):1039-1045.
[15] MIN L,ZHANG C,MA R L,et al. Over expression of synuclein-γ predicts lack of benefit from radiotherapy for breast cancer patients[J]. BMC Cancer,2016,16:717.
[16] 张荣繁,斯琴高娃,新燕,等. SurvivinsiRNA、HSP70双基因转染对乳腺癌细胞株MCF7 survivin及HSP70表达的影响[J]. 疾病监测与控制,2014(5):275-276.
[17] ZHUANG Q,LIU C,QU L,et al. Synuclein-γ promotes migration of MCF7 breast cancer cells by activating extra-cellular-signal regulated kinase pathway and breaking cell-cell junctions[J]. Mol Med Rep,2015,12(3):3795-3800.

Activation of mTOR signaling pathway can reduce radiation sensitivity through up-regulating SNCG expression in breast cancer cells

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