PI3K/AKT/mTOR/p70S6K通路在人舌鳞癌细胞耐药中的作用

doi:10.13701/j.cnki.kqyxyj.2017.09.007

口腔医学研究 ›› 2017, Vol. 33 ›› Issue (9): 938-942.DOI: 10.13701/j.cnki.kqyxyj.2017.09.007

PI3K/AKT/mTOR/p70S6K通路在人舌鳞癌细胞耐药中的作用

章思莹¹，潘淑婷¹，帅芳源²，邱嘉旋^1*

1. 南昌大学第一附属医院口腔颌面外科江西南昌 330006；
2. 四川大学华西口腔医学院四川成都 610041

收稿日期:2017-02-27 出版日期:2017-09-20 发布日期:2017-09-27
通讯作者: 邱嘉旋,E-mail:qiujiaxuan@163.com
作者简介:章思莹(1992~ ),女,江西南昌人,硕士,主要从事口腔颌面外科临床治疗工作。
基金资助:
江西省科技厅自然科学基金重大项目(编号:20152ACB20019)

Role of PI3K/AKT/mTOR/p70S6K Pathway in Drug Resistance of Tongue Squamous Cells

ZHANG Si-ying¹, PAN Shu-ting¹, SHUAI Fang-yuan², QIU Jia-xuan^1*

1. Department of Oral＆Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University. Nanchang 330006, China;
2. West China School of Stomatology, Sichuan University. Chengdu 610041, China.

Received:2017-02-27 Online:2017-09-20 Published:2017-09-27

摘要/Abstract

摘要： 目的:通过抑制舌鳞癌细胞中PI3K/AKT/mTOR/p70S6K信号通路的表达,检测细胞凋亡与自噬的变化,探讨舌鳞癌耐药的机制。方法:以舌鳞癌细胞Cal27与舌鳞癌耐顺铂细胞Cal27/CDDP为研究对象。分别用PI3K/AKT抑制剂LY294002、mTOR抑制剂Rapamycin、p70S6K抑制剂LY2584702作用该通路各个环节。Western blot检测通路抑制剂作用后相关蛋白的变化。Cyto-ID荧光染色检测自噬体的形成。流式细胞术检测细胞凋亡水平。结果:Western blot结果显示加入抑制剂后舌鳞癌细胞Beclin1表达分别高于对照组,LC3II与LC3I以及Bax与Bcl-2的比值均升高,该通路的p-AKT、p-mTOR、p-p70S6K等蛋白均有下降(P<0.05)。流式结果显示加入抑制剂后的舌鳞癌细胞凋亡率分别较对照组升高(P<0.05)。Cyto-ID荧光染色后结果显示加入抑制剂后的舌鳞癌细胞自噬小体的数目明显高于对照组(P<0.05)。对比两组细胞显示加入抑制剂后的Cal27细胞发生凋亡与自噬的水平高于Cal27/CDDP(P<0.05)。结论:抑制PI3K/AKT/mTOR/p70S6K信号通路可诱导舌鳞癌细胞Cal27与舌鳞癌耐顺铂细胞Cal27/CDDP发生凋亡与自噬,激活的PI3K/AKT/mTOR/p70S6K通路抑制细胞凋亡与自噬是Cal27/CDDP细胞产生顺铂耐药的原因之一。

关键词: 舌鳞癌, PI3K/AKT/mTOR/p70S6K, 顺铂耐药, 自噬, 凋亡

Abstract: Objective: To investigate the role of PI3K/AKT/mTOR/p70S6K signaling pathway in drug resistance of tongue squamous cells. Methods: Tongue squamous cell carcinoma line Cal27 and tongue squamous cell carcinoma cell line Cal27/CDDP with cisplatin resistance were repeatedly treated with the specific inhibitor, LY294002 (PI3K/AKT inhibitor) , Rapamycin (mTOR inhibitor), and LY2584702 (p70S6K inhibitor). Related proteins in PI3K/AKT/mTOR/p70S6K pathway were detected by Western blot. The level of autophagy was detected with Cyto-ID fluorescence staining. Cellular apoptosis was detected by flow cytometry. Results: After applying the pathway inhibitors, the expression level of Beclin1 of the tongue squamous cells were enhanced compared with the control group. Moreover, the ratio of the LC3II to LC3I and the ratio of the Bax to Bcl-2 were increased. The expression of p-AKT, p-mTOR, and p-p70S6K were decreased (P<0.05). The apoptosis and autophagy level were increased in tongue squamous cells, compared with control group. Conclusion: Inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway shows a significant effect on apoptosis and autophagy in Cal27 and Cal27/CDDP.

Key words: Tongue squamous cells, PI3K/AKT/mTOR/p70S6K, Cisplatin resistance, Autophagy, Apoptosis

中图分类号:

R739.8

章思莹，潘淑婷，帅芳源，邱嘉旋. PI3K/AKT/mTOR/p70S6K通路在人舌鳞癌细胞耐药中的作用[J]. 口腔医学研究, 2017, 33(9): 938-942.

ZHANG Si-ying, PAN Shu-ting, SHUAI Fang-yuan, QIU Jia-xuan. Role of PI3K/AKT/mTOR/p70S6K Pathway in Drug Resistance of Tongue Squamous Cells[J]. Journal of Oral Science Research, 2017, 33(9): 938-942.

参考文献

[1] Isa&xe, Waal CVD. Are we able to reduce the mortality and morbidity of oral cancer; Some considerations [J]. Medicina Oral Patologia Oral Y CirugiaBucal, 2013, 18(1)∶33-37
[2] Richard V, Sebastian P, Nair MG, et al. Multiple drug resistant, tumorigenic stem-like cells in oral cancer [J]. Cancer Letters, 2013, 338(2)∶300-316
[3] 马壮, 张胜, 朱郁文,等.人舌鳞癌细胞SOCS1基因沉默对细胞增殖和化疗药物敏感性的影响[J].口腔医学研究,2015,31(3)∶283-286
[4] Jiang BH. PI3K/AKT and mTOR/p70S6K1 signaling pathways in human cancer [J]. Current Cancer Drug Targets,2013,13(3)∶233-237
[5] Ni J, Cozzi P, Hao J, et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radio resistance via the PI3K/Akt/mTOR signaling pathway [J]. International Journal of Biochemistry & Cell Biology, 2013, 45(12)∶2736-2748
[6] 刘墨,张斌,王安训,等.人舌鳞状细胞癌顺铂耐药细胞发生上皮-间质转化的研究[J].中华口腔医学研究杂志电子版,2014(5)∶5-9
[7] Pan S, Li Z, He Z, et al. Molecular mechanisms for tumor resistance to chemotherapy [J]. Clinical & Experimental Pharmacology & Physiology, 2016, 43(8)∶723-737
[8] Laplante M, Sabatini D M. mTOR signaling in growth control and disease [J]. Cell, 2012, 149(2)∶274-293
[9] Cai Y, Tan X, Liu J, et al. Inhibition of PI3K/Akt/mTOR signaling pathway enhances the sensitivity of the SKOV3/DDP ovarian cancer cell line to cisplatin in vitro [J]. 中国癌症研究(英文版), 2014, 26(5)∶564-572
[10] Vanhaesebroeck B, Vogt PK, Rommel C. PI3K: from the bench to the clinic and back [J]. Current Topics in Microbiology & Immunology, 2010, 347(1)∶1-19
[11] Weichhart T, S emann M D. The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications [J]. Annals of the rheumatic diseases, 2008, 67 Suppl 3(6)∶70-74
[12] Wang RC, Wei Y, An Z, et al. Akt-Mediated Regulation of Autophagy and Tumorigenesis Through Beclin 1 Phosphorylation [J]. Science, 2012, 338(6109)∶956
[13] Zhang Q, Zhu H, Xu X, et al. Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells [J]. Biochemical & Biophysical Research Communications, 2015, 465(1)∶64-70
[14] Peng DJ, Zhou WJY, Wu GS. Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells [J]. Biochemical & Biophysical Research Communications, 2010, 394(3)∶600-605

[1]	齐晓爽, 孟维艳. 用于牙周炎治疗的自噬调节物研究现状[J]. 口腔医学研究, 2020, 36(7): 616-618.
[2]	梁德凤, 周鑫才, 吴芸菲. 二甲双胍调节PI3K/AKT通路对高糖诱导牙周膜成纤维细胞凋亡的影响研究[J]. 口腔医学研究, 2020, 36(12): 1103-1107.
[3]	周洋. 微小RNA-218-5p靶向TLR2基因对LPS所致人牙周膜干细胞炎症反应的影响[J]. 口腔医学研究, 2020, 36(12): 1108-1112.
[4]	黄佩, 乔玮玮, 孟柳燕. 自噬通过GATA4调控人牙髓细胞衰老反应[J]. 口腔医学研究, 2020, 36(12): 1142-1147.
[5]	周群, 邱嘉旋. 白花丹素通过ROS介导的JNK通路诱导舌鳞状细胞癌细胞凋亡[J]. 口腔医学研究, 2020, 36(10): 921-924.
[6]	毛家奇, 黄蔚, 於丽明, 赵力如, 杨冬茹, 卢芸. 低氧对C2C12细胞分化不同阶段自噬和肌细胞生成素表达的影响[J]. 口腔医学研究, 2020, 36(1): 70-74.
[7]	谢龙, 桑磊, 宋卓英, 江燕军. 唾液中微小RNA-375对口腔鳞状细胞癌的诊断价值及其对人口腔鳞状细胞癌细胞生物学功能的影响[J]. 口腔医学研究, 2019, 35(9): 883-888.
[8]	邓轩, 阳芳, 唐西清. 下调黏蛋白1对人舌鳞状细胞癌Tca-8113细胞裸鼠皮下移植瘤生长的影响[J]. 口腔医学研究, 2019, 35(8): 776-780.
[9]	单秋生, 李国林, 许嘉琪. TH287对口腔鳞状细胞癌CAL27细胞增殖和迁移的抑制作用[J]. 口腔医学研究, 2019, 35(7): 704-707.
[10]	陈杰,徐华兴,程抒华,张旗. 细胞自噬在牙髓损伤修复过程中的作用[J]. 口腔医学研究, 2019, 35(6): 531-536.
[11]	王蕊,李立恒,胥爱文,安峰. 慢病毒介导的Med19表达下调提高舌鳞癌细胞顺铂敏感性[J]. 口腔医学研究, 2019, 35(6): 559-562.
[12]	周童,张桐菲,张泽兵,全海英. 甲基硒酸对口腔癌细胞增殖、迁移、凋亡和周期的作用研究[J]. 口腔医学研究, 2019, 35(6): 568-572.
[13]	张馨予, 吴双燕, 吴鸿, 徐竹青, 王云英, 徐晓娜, 李新, 郑建金. 人脐带间充质干细胞对舌鳞状细胞癌Cal-27细胞侵袭和迁移能力的影响[J]. 口腔医学研究, 2019, 35(5): 443-447.
[14]	孙维克, 王培源, 刘伟, 王霞. Beclin1与凋亡相关蛋白在口腔鳞癌中的表达及意义[J]. 口腔医学研究, 2019, 35(10): 979-983.
[15]	裴浩, 李海朋, 黄莹莹, 马钊. β-谷甾醇诱导口腔鳞状细胞癌SCC9细胞凋亡及机制研究[J]. 口腔医学研究, 2019, 35(1): 42-45.

PI3K/AKT/mTOR/p70S6K通路在人舌鳞癌细胞耐药中的作用

Role of PI3K/AKT/mTOR/p70S6K Pathway in Drug Resistance of Tongue Squamous Cells

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics