切换至 "中华医学电子期刊资源库"

中华口腔医学研究杂志(电子版) ›› 2016, Vol. 10 ›› Issue (06) : 372 -376. doi: 10.3877/cma.j.issn.1674-1366.2016.06.002

所属专题: 文献

基础研究

低氧增强自噬促进舌鳞状细胞癌细胞迁移和侵袭
陈冠辉1, 王成1, 翁军权1, 梁建锋1, 李文清1, 竺越1, 侯劲松1,()   
  1. 1. 510055 广州,中山大学光华口腔医学院·附属口腔医院,广东省口腔医学重点实验室
  • 收稿日期:2016-10-12 出版日期:2016-12-01
  • 通信作者: 侯劲松
  • 基金资助:
    国家自然科学基金(81572660); 广东省自然科学基金(2015A030313034); 广东省科技计划(2013B021800059); 中山大学临床医学研究5010计划(2015018)

Hypoxia induced autophagy and promotes the migration and invasion in tongue squamous cell carcinoma

Guanhui Chen1, Cheng Wang1, Junquan Weng1, Jianfeng Liang1, Wenqing Li1, Yue Zhu1, Jinsong Hou1,()   

  1. 1. Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
  • Received:2016-10-12 Published:2016-12-01
  • Corresponding author: Jinsong Hou
  • About author:
    Corresponding author: Hiu Jinsong, Email:
引用本文:

陈冠辉, 王成, 翁军权, 梁建锋, 李文清, 竺越, 侯劲松. 低氧增强自噬促进舌鳞状细胞癌细胞迁移和侵袭[J/OL]. 中华口腔医学研究杂志(电子版), 2016, 10(06): 372-376.

Guanhui Chen, Cheng Wang, Junquan Weng, Jianfeng Liang, Wenqing Li, Yue Zhu, Jinsong Hou. Hypoxia induced autophagy and promotes the migration and invasion in tongue squamous cell carcinoma[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2016, 10(06): 372-376.

目的

探讨低氧条件下对舌鳞状细胞癌(TSCC)自噬活性和迁移能力的影响。

方法

应用含1% O2的低氧培养箱培养TSCC UM1细胞,Western blot检测低氧诱导3、6、9、12、24 h后低氧诱导因子1α(HIF-1α)和自噬标记蛋白Beclin-1、自噬相关蛋白5(ATG5)和微管相关蛋白轻链3(LC3)的表达变化;细胞划痕实验检测低氧诱导后细胞迁移能力的改变;Transwell侵袭小室实验检测低氧诱导后细胞的侵袭能力;SPSS 13.0统计软件进行数据分析。

结果

低氧条件下,与对照组(0.527 ± 0.055)相比,TSCC UM1细胞自噬体双层膜标记蛋白LC3Ⅱ的表达(1.206 ± 0.053)增加(t= 12.96,P<0.001),同时自噬相关蛋白Beclin-1表达量(1.151 ± 0.078)较对照组(0.775 ± 0.062)明显提高(t= 6.736,P= 0.001),ATG5的表达(1.231 ± 0.06)较对照组(0.711 ± 0.052)也明显上升(t= 7.834,P= 0.001)。与对照组相比,低氧诱导后细胞迁移能力(0.349 ± 0.024)较对照组(0.788 ± 0.037)明显增加(t= 9.918,P= 0.001),细胞侵袭能力(23 ± 2)较对照组(71 ± 4)明显增强(t= 9.528,P= 0.001)。

结论

低氧条件下可以增强TSCC细胞自噬活性,促进其迁移和侵袭。

Objective

To investigate the effect of hypoxia on autophagy and migration of tongue squamous cell carcinoma (TSCC) cell line.

Methods

UM1 cells were cultured in hypoxia incubator containing 1% oxygen concentration. Western blot was performed to examine the expression of HIF-1α, Beclin-1, ATG5 and LC3 following 3, 6, 9, 12 and 24 h of treatment of hypoxia. Wounding healing was used to evaluate cell migration. Transwell assay was carried out to assess cell invasion. Statistical analysis was performed using SPSS 13.0 software.

Results

After, The expression level of autophagic protein LC3Ⅱ (1.206 ± 0.053) in the hypoxia treatment group was higher than control group (0.527 ± 0.055) and both showed statistically significant difference (t= 12.96, P<0.001) ; the expression level of Beclin-1 (1.151 ± 0.078) in the hypoxia treatment group was higher than control group (0.775 ± 0.062) , and both showed a statistically significant difference (t= 6.736, P= 0.001) ; the expression level of ATG5 (1.231 ± 0.06) in the hypoxia treatment group was higher than control group (0.711 ± 0.052) , was and both showed a statistically significant difference (t= 7.834, P= 0.001) . The migration ability of TSCCUM1 (0.349 ± 0.024) was improved under hypoxia in comparison to control groups (0.788 ± 0.037) (t= 9.918, P= 0.001) . The invasion ability of TSCCUM1 (23 ± 2) was upregulated under hypoxia in comparison to control groups (71 ± 4) (t= 9.528, P= 0.001) .

Conclusion

Hypoxia can improve autophagic activity levels and promotes the migration and invasion in tongue squamous cell carcinoma cell line.

图1 低氧处理不同时间后舌鳞状细胞癌细胞自噬相关蛋白表达变化
图2~5 低氧处理不同时间点后舌鳞状细胞癌细胞自噬相关蛋白相对表达变化
图6 低氧处理24 h后舌鳞状细胞癌UM1细胞迁移情况(× 50)
图7 低氧处理24 h后舌鳞状细胞癌UM1细胞划痕愈合率相对变化
图8 低氧处理后舌鳞状细胞癌细胞侵袭能力比较(× 100)
[1]
Lee J, Giordano S, Zhang J. Autophagy,mitochondria and oxidative stress:cross-talk and redox signalling[J]. Biochem J,2012,441(2):523-540.
[2]
Mizushima N, Komatsu M. Autophagy:renovation of cells and tissues[J]. Cell,2011,147(4):728-741.
[3]
Rouschop KM, Wouters BG. Regulation of autophagy through multiple independent hypoxic signaling pathways[J]. Curr Mol Med,2009,9(4):417-424.
[4]
Wu H, Huang S, Chen Z,et al. Hypoxia-induced autophagy contributes to the invasion of salivary adenoid cysticcarcinoma through the HIF-1α/BNIP3 signaling pathway[J]. Mol Med Rep,2015,12(5):6467-6474.
[5]
Liu XW, Cai TY, Zhu H,et al. Q6,a novel hypoxia-targeted drug,regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma[J]. Autophagy,2014,10(1):111-122.
[6]
Maiuri MC, Zalckvar E, Kimchi A,et al. Self-eating and self-killing:crosstalk between autophagy and apoptosis[J]. Nat Rev Mol Cell Biol,2007,8(9):741-752.
[7]
Martinet W, Agostinis P, Vanhoecke B,et al. Autophagy in disease:a double-edged sword with therapeutic potential[J]. Clin Sci(Lond),2009,116(9):697-712.
[8]
Toustrup K, Sorensen BS, Alsner J,et al. Hypoxia gene expression signatures as prognostic and predictive markers in head and neck radiotherapy[J]. Semin Radiat Oncol,2012,22(2):119-127.
[9]
Wu H, Huang S, Zhang D. Autophagic responses to hypoxia and anticancer therapy in head and neck cancer[J]. Pathol Res Pract,2015,211(2):101-108.
[10]
Blasiak J, Petrovski G, Veréb Z,et al. Oxidative stress,hypoxia,and autophagy in the neovascular processes of age-related macular degeneration[J]. Biomed Res Int,2014(2014):768026.
[11]
Brennan PA, Mackenzie N, Quintero M. Hypoxia-inducible factor 1alpha in oral cancer[J]. J Oral Pathol Med,2005,34(7):385-389.
[12]
Vaupel P, Mayer A. Hypoxia in cancer:significance and impact on clinical outcome[J]. Cancer Metastasis Rev,2007,26(2):225-239.
[13]
Zhao X, He Y, Chen H. Autophagic tumor stroma:mechanisms and roles in tumor growth and progression[J]. Int J Cancer,2013,132(1):1-8.
[14]
Jiang H, Cheng D, Liu W,et al. Protein kinase C inhibits autophagy and phosphorylates LC3[J]. Biochem Biophys Res Commun,2010,395(4):471-476.
[15]
Suzuki K, Ohsumi Y. Molecular machinery of autophagosome formation in yeast,Saccharomycescerevisiae[J]. FEBS Lett,2007,581(11):2156-2161.
[16]
Mizushima N, Kuma A, Kobayashi Y,et al. Mouse Apg16L,a novel WD-repeat protein,targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate[J]. J Cell Sci,2003,116(Pt 9):1679-1688.
[17]
Yamanaka-Tatematsu M, Nakashima A, Fujita N,et al. Autophagy induced by HIF1α overexpression supports trophoblast invasion by supplying cellular energy[J]. PLoS One,2013,8(10):e76605.
[18]
Thongchot S, Yongvanit P, Loilome W,et al. High expression of HIF-1α,BNIP3 and PI3KC3:hypoxia-induced autophagy predicts cholangiocarcinoma survival and metastasis[J]. Asian Pac J Cancer Prev,2014,15(14):5873-5878.
[19]
Laderoute KR, Amin K, Calaoagan JM,et al. 5′-AMP-activated protein kinase(AMPK)is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments[J]. Mol Cell Biol,2006,26(14):5336-5347.
[1] 张刚, 秦勇, 黄超, 薛震, 吕松岑. 基于骨关节炎软骨细胞表型转化的新兴治疗靶点[J/OL]. 中华关节外科杂志(电子版), 2024, 18(03): 352-362.
[2] 吴杰, 周志强, 符菁, 李喜功, 张钦. 吸入性氢气对大鼠脊髓损伤后自噬及神经功能的影响[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(05): 363-371.
[3] 许彬, 王丽, 陈瑞, 沈奕, 陆件. 瞬时受体电位粘脂素1介导细胞自噬在远端缺血后处理保护大鼠脑缺血-再灌注损伤中的作用研究[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(03): 180-187.
[4] 李争光, 宰爽嘉, 吴火峰, 孙华, 张永博, 陈浏阳, 戴睿, 张亮. 昼夜节律相关因子在椎间盘退行性变发病机制中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(05): 457-461.
[5] 陈金业, 凌潜龙, 朱冰, 骆杰. 补体B因子在结直肠癌中的表达及临床意义[J/OL]. 中华普通外科学文献(电子版), 2024, 18(03): 192-198.
[6] 张敏龙, 杨翠平, 王博, 崔云杰, 金发光. MiR-200b-3p 通过抑制HIF-1α 表达减轻海水吸入诱导的肺水肿作用及机制[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 696-700.
[7] 赵蒙蒙, 黄洁, 余荣环, 王葆青. 过表达小GTP酶Rab32抑制非小细胞肺癌细胞侵袭性生长[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 512-518.
[8] 赵旭鹏, 王集琛, 田硕, 李宏召, 李修彬, 张旭. EP300 通过上调FKBP10 促进膀胱肿瘤细胞迁移和侵袭[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 264-274.
[9] 曾聿理, 雷发容, 肖慧, 邱德亮, 谢静, 吴寻. 氯普鲁卡因通过调控circRNA-ZKSCAN1表达抑制肝癌Huh-7细胞体外生长和转移的研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 220-228.
[10] 崔精, 鲍一帆, 沈晓明, 杨增辉, 高森, 鲍传庆. 结直肠癌中circMFSD12对肿瘤细胞功能及5-FU敏感性的调控[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 294-302.
[11] 王国强, 张纲, 唐建坡, 张玉国, 杨永江. LINC00839 调节miR-17-5p/WEE1 轴对结直肠癌细胞增殖、凋亡和迁移的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 491-499.
[12] 史清泉, 苗彬, 王烁, 陶琳, 沈晨. miR-181a-5p 靶向ATG5 抑制雨蛙素诱导的大鼠胰腺腺泡细胞AR42J自噬的机制研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 524-530.
[13] 朱镭, 朱庆义. 金氏菌属:引起婴幼儿侵袭性传染病的新发病原体[J/OL]. 中华临床实验室管理电子杂志, 2024, 12(04): 229-237.
[14] 张芳芳, 李军, 赵玉洁, 于彤, 宁春平. 侵袭性血管黏液瘤的影像学特征并文献复习[J/OL]. 中华诊断学电子杂志, 2024, 12(04): 254-259.
[15] 刘霖, 张文欢, 宋雅茹, 姜云璐. Apelin-13 在阿尔茨海默病中的神经保护作用机制研究进展[J/OL]. 中华诊断学电子杂志, 2024, 12(04): 276-280.
阅读次数
全文


摘要