口腔医学 ›› 2025, Vol. 45 ›› Issue (12): 951-955.doi: 10.13591/j.cnki.kqyx.2025.12.013
陈睿业1, 刘懿卿1, 张鹭1, 陈宇钊1, 邱峰2,3(
)
收稿日期:2024-12-16
出版日期:2025-12-28
发布日期:2025-12-16
通讯作者:
邱峰
E-mail:qiufeng0773@foxmail.com
基金资助:
CHEN Ruiye1, LIU Yiqing1, ZHANG Lu1, CHEN Yuzhao1, QIU Feng2,3(
)
Received:2024-12-16
Online:2025-12-28
Published:2025-12-16
Contact:
QIU Feng
E-mail:qiufeng0773@foxmail.com
摘要:
口腔癌是最常见的恶性肿瘤之一,其中约90%为鳞状细胞癌(OSCC)。该病生长迅速,浸润性强,复发率高且易转移,严重威胁着人类健康。近年来研究表明,NF-κB信号通路的异常激活与OSCC的发生发展密切相关。本文探讨了NF-κB信号通路在口腔鳞癌中的多途径调控作用,包括影响炎症反应、细胞增殖、凋亡、侵袭转移及耐药等,并分析了针对NF-κB信号通路作为潜在治疗靶点的OSCC治疗策略与药物开发前景。
中图分类号:
陈睿业, 刘懿卿, 张鹭, 陈宇钊, 邱峰. NF-κB信号通路在口腔鳞状细胞癌中作用的研究进展[J]. 口腔医学, 2025, 45(12): 951-955.
CHEN Ruiye, LIU Yiqing, ZHANG Lu, CHEN Yuzhao, QIU Feng. Research progress of the role of NF-κB signaling pathway in oral squamous cell carcinoma[J]. Stomatology, 2025, 45(12): 951-955.
| [1] | 张陈平, 王磊. 口腔癌的侵袭前缘及外科根治策略[J]. 口腔医学, 2022, 42(11):961-965. |
| [2] | 邱峰. Oct4和Sox2通过影响RHEBL1的表达对口腔鳞状细胞癌发生和增殖作用的实验研究[D]. 郑州: 郑州大学, 2021. |
| [3] | [ Mumlek I, Ozretić P, Sabol M, et al. BIRC5 gene polymorphisms are associated with a higher stage of local and regional disease in oral and oropharyngeal squamous cell carcinomas[J]. Int J Mol Sci, 2023, 24(24):17940. |
| [4] |
Jiang XG, Wu JX, Wang JX, et al. Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways[J]. Tob Induc Dis, 2019, 17: 29.
doi: 10.18332/tid/105844 pmid: 31582940 |
| [5] | Saranya R, Chandini R, Mohideen K, et al. Expression of sex hormones in oral squamous cell carcinoma: A systematic review on immunohistochemical studies[J]. Cureus, 2022, 14(5): e25384. |
| [6] |
Melo BAC, Vilar LG, Oliveira NR, et al. Human papillomavirus infection and oral squamous cell carcinoma: A systematic review[J]. Braz J Otorhinolaryngol, 2021, 87(3): 346-352.
doi: 10.1016/j.bjorl.2020.10.017 |
| [7] |
Di Spirito F, Di Palo MP, Folliero V, et al. Oral bacteria, virus and fungi in saliva and tissue samples from adult subjects with oral squamous cell carcinoma: An umbrella review[J]. Cancers (Basel), 2023, 15(23): 5540.
doi: 10.3390/cancers15235540 |
| [8] |
Pillai A, Adilbay D, Matsoukas K, et al. Autoimmune disease and oral squamous cell carcinoma: A systematic review[J]. J Oral Pathol Med, 2021, 50(9): 855-863.
doi: 10.1111/jop.v50.9 |
| [9] |
Mudianto T, Campbell KM, Webb J, et al. Yap1 mediates trametinib resistance in head and neck squamous cell carcinomas[J]. Clin Cancer Res, 2021, 27(8): 2326-2339.
doi: 10.1158/1078-0432.CCR-19-4179 pmid: 33547198 |
| [10] | 张万林, 李一村, 杨宏宇. 基于RNA-Seq技术初步探索顺铂在口腔鳞状细胞癌的相关耐药机制[J]. 遵义医科大学学报, 2024, 47(1): 53-61. |
| [11] |
Shi YW, Ren XY, Cao SL, et al. TP53 gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma[J]. J Immunother Cancer, 2023, 11(8): e006666.
doi: 10.1136/jitc-2023-006666 |
| [12] |
Padhi SS, Roy S, Kar M, et al. Role of CDKN2A/p16 expression in the prognostication of oral squamous cell carcinoma[J]. Oral Oncol, 2017, 73: 27-35.
doi: S1368-8375(17)30220-8 pmid: 28939073 |
| [13] |
Mohammedsaleh ZM, Moawadh MS, Saleh FM, et al. Increased NOTCH1 expression is associated with low survival in moderate/poor differentiated human oral squamous cell carcinoma patients[J]. J Cancer, 2023, 14(16): 3023-3027.
doi: 10.7150/jca.87128 pmid: 37859809 |
| [14] | 李娜, 邓茜. NF-κB信号通路在恶性肿瘤化疗耐药中的作用[J]. 实用肿瘤学杂志, 2021, 35(6): 580-584. |
| [15] |
Cho H, Thorvaldsen JL, Chu Q, et al. Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice[J]. J Biol Chem, 2001, 276(42): 38349-38352.
doi: 10.1074/jbc.C100462200 pmid: 11533044 |
| [16] | 陈婷婷. 作用于NF-κB信号通路的肽类衍生物的合成及抗炎和抗辐射活性研究[D]. 北京: 军事科学院, 2023. |
| [17] |
Li ZW, Chu W, Hu Y, et al. The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis[J]. J Exp Med, 1999, 189(11): 1839-1845.
doi: 10.1084/jem.189.11.1839 pmid: 10359587 |
| [18] | Yu H, Lin LB, Zhang ZQ, et al. Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study[J]. Signal Transduct Target Ther, 2020, 5(1): 209. |
| [19] |
贺欣然, 李元, 张武阳, 等. 牙周炎中巨噬细胞极化、焦亡、胞葬的研究进展[J]. 口腔疾病防治, 2024, 32(11):886-893.
doi: 10.12016/j.issn.2096-1456.202330511 |
| [20] |
Meyer-Hermann M, Mohr E, Pelletier N, et al. A theory of germinal center B cell selection, division, and exit[J]. Cell Rep, 2012, 2(1): 162-174.
doi: 10.1016/j.celrep.2012.05.010 pmid: 22840406 |
| [21] |
Baldwin AS. Regulation of cell death and autophagy by IKK and NF-κB: Critical mechanisms in immune function and cancer[J]. Immunol Rev, 2012, 246(1): 327-345.
doi: 10.1111/j.1600-065X.2012.01095.x pmid: 22435564 |
| [22] | Kamperos G, Nikitakis N, Sfakianou A, et al. Expression of NF-κB and IL-6 in oral precancerous and cancerous lesions: An immunohistochemical study[J]. Med Oral Patol Oral Cir Bucal, 2016, 21(1): e6-13. |
| [23] |
Babiuch K, Kuśnierz-Cabala B, Kęsek B, et al. Evaluation of proinflammatory, NF-kappaB dependent cytokines: IL-1α, IL-6, IL-8, and TNF-α in tissue specimens and saliva of patients with oral squamous cell carcinoma and oral potentially malignant disorders[J]. J Clin Med, 2020, 9(3): 867.
doi: 10.3390/jcm9030867 |
| [24] |
Sun ST, Yang HY, Wang F, et al. Oct4 downregulation-induced inflammation increases the migration and invasion rate of oral squamous cell carcinoma[J]. Acta Biochim Biophys Sin (Shanghai), 2021, 53(11): 1440-1449.
doi: 10.1093/abbs/gmab127 |
| [25] |
Sordi MB, Panahipour L, Gruber R. Oral squamous carcinoma cell lysates provoke exacerbated inflammatory response in gingival fibroblasts[J]. Clin Oral Investig, 2023, 27(8): 4785-4794.
doi: 10.1007/s00784-023-05107-x |
| [26] |
Sinto MS, Thomas S, Kannan S. Combinatorial treatment with Gefitinib and Bay11-7085 sensitizes primary Gefitinib-resistant OSCC cells by influencing the EGFR-NFκB signaling axis[J]. Med Oncol, 2021, 38(9): 110.
doi: 10.1007/s12032-021-01557-z pmid: 34357463 |
| [27] |
Bordoloi D, Monisha J, Roy NK, et al. An investigation on the therapeutic potential of butein, a tretrahydroxychalcone against human oral squamous cell carcinoma[J]. Asian Pac J Cancer Prev, 2019, 20(11): 3437-3446.
doi: 10.31557/APJCP.2019.20.11.3437 |
| [28] |
Shi LJ, Yang YQ, Li MY, et al. LncRNA IFITM4P promotes immune escape by up-regulating PD-L1 via dual mechanism in oral carcinogenesis[J]. Mol Ther, 2022, 30(4): 1564-1577.
doi: 10.1016/j.ymthe.2022.01.003 |
| [29] |
Hinz M, Krappmann D, Eichten A, et al. NF-kappaB function in growth control: Regulation of cyclin D1 expression and G0/G1-to-S-phase transition[J]. Mol Cell Biol, 1999, 19(4): 2690-2698.
doi: 10.1128/MCB.19.4.2690 pmid: 10082535 |
| [30] |
Du YX, Yang YL, Zhang WB, et al. Human β-defensin-3 and nuclear factor-kappa B p65 synergistically promote the cell proliferation and invasion of oral squamous cell carcinoma[J]. Transl Oncol, 2023, 27: 101582.
doi: 10.1016/j.tranon.2022.101582 |
| [31] |
Elmore S. Apoptosis: A review of programmed cell death[J]. Toxicol Pathol, 2007, 35(4): 495-516.
doi: 10.1080/01926230701320337 pmid: 17562483 |
| [32] |
Zhang YQ, Yuan Y, Wu HM, et al. Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma[J]. Int J Cancer, 2018, 143(4): 980-991.
doi: 10.1002/ijc.31378 pmid: 29536537 |
| [33] |
Veisi A, Akbari G, Mard SA, et al. Role of crocin in several cancer cell lines: An updated review[J]. Iran J Basic Med Sci, 2020, 23(1): 3-12.
doi: 10.22038/IJBMS.2019.37821.8995 pmid: 32405344 |
| [34] |
Yoshimatsu Y, Wakabayashi I, Kimuro S, et al. TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation[J]. Cancer Sci, 2020, 111(7): 2385-2399.
doi: 10.1111/cas.v111.7 |
| [35] |
Tang DF, Tao DT, Fang Y, et al. TNF-alpha promotes invasion and metastasis via NF-kappa B pathway in oral squamous cell carcinoma[J]. Med Sci Monit Basic Res, 2017, 23: 141-149.
doi: 10.12659/MSMBR.903910 |
| [36] |
Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances[J]. Sensors (Basel), 2018, 18(10): 3249.
doi: 10.3390/s18103249 |
| [37] |
Ideta Y, Tagawa T, Hayashi Y, et al. Transcriptomic profiling predicts multiple pathways and molecules associated with the metastatic phenotype of oral cancer cells[J]. Cancer Genomics Proteomics, 2021, 18(1): 17-27.
doi: 10.21873/cgp.20238 |
| [38] |
Jiang MJ, Gu DN, Dai JJ, et al. Dark side of cytotoxic therapy: Chemoradiation-induced cell death and tumor repopulation[J]. Trends Cancer, 2020, 6(5): 419-431.
doi: 10.1016/j.trecan.2020.01.018 |
| [39] |
Jia XT, Wang G, Wu LH, et al. XBP1-elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR-22/lncRNA/KAT6B-dependent NF-κB signalling[J]. Clin Transl Med, 2023, 13(1): e1166.
doi: 10.1002/ctm2.1166 pmid: 36639835 |
| [40] |
Huang ZX, Zhang Y, Li HG, et al. Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3[J]. Cell Death Dis, 2019, 10(12): 936.
doi: 10.1038/s41419-019-2177-x pmid: 31819048 |
| [41] |
Alam M, Kashyap T, Pramanik KK, et al. The elevated activation of NFκB and AP-1 is correlated with differential regulation of Bcl-2 and associated with oral squamous cell carcinoma progression and resistance[J]. Clin Oral Investig, 2017, 21(9): 2721-2731.
doi: 10.1007/s00784-017-2074-6 |
| [42] |
Labbozzetta M, Notarbartolo M, Poma PL. Can NF-κB be considered a valid drug target in neoplastic diseases? Our point of view[J]. Int J Mol Sci, 2020, 21(9): 3070.
doi: 10.3390/ijms21093070 |
| [43] | Yu JS, Huang T, Zhang Y, et al. Substrate-specific recognition of IKKs mediated by USP16 facilitates autoimmune inflammation[J]. Sci Adv, 2021, 7(3): eabc4009. |
| [44] |
Pires BRB, Silva RCMC, Ferreira GM, et al. NF-kappaB: Two sides of the same coin[J]. Genes (Basel), 2018, 9(1): 24.
doi: 10.3390/genes9010024 |
| [45] | 于澜, 徐俊超, 郑佳连, 等. 基于网络药理学探讨红曲-山楂治疗NASH的作用机制及关于NF-κB信号通路的机制验证[J]. 浙江中医药大学学报, 2023, 47(9): 986-1001. |
| [46] | 王天明, 车莹, 崔岩, 等. NF-κB(p50/p65)介导的促炎微小RNA信号转导在金黄色葡萄球菌感染中的作用[J]. 中国感染控制杂志, 2023, 22(10): 1260-1265. |
| [47] |
Gaczynska M, Osmulski PA. Targeting protein-protein interactions in the ubiquitin-proteasome pathway[J]. Adv Protein Chem Struct Biol, 2018, 110: 123-165.
doi: S1876-1623(17)30065-2 pmid: 29412995 |
| [48] | 王慧哲, 胡晓龙, 汪豪. 环氧合酶-2抑制剂的研究进展[J]. 西北药学杂志, 2021, 36(6): 1019-1026. |
| [49] | 朱乐. ATPR联合Cox-2抑制剂对下咽癌FaDu细胞生物学行为的影响及其机制研究[D]. 合肥: 安徽医科大学, 2020. |
| [50] |
Su J, Zhao PJ, Kong LM, et al. Trichothecin induces cell death in NF-κB constitutively activated human cancer cells via inhibition of IKKβ phosphorylation[J]. PLoS One, 2013, 8(8): e71333.
doi: 10.1371/journal.pone.0071333 |
| [51] |
Alavi M, Farkhondeh T, Aschner M, et al. Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation[J]. Cancer Cell Int, 2021, 21(1): 579.
doi: 10.1186/s12935-021-02280-5 pmid: 34717625 |
| [52] |
李少鹏, 杨海燕, 张力, 等. 白藜芦醇通过NF-κB相关通路对顺铂引起的OSCC细胞化疗耐药性的影响[J]. 口腔颌面外科杂志, 2024, 34(2): 94-99.
doi: 10.12439/kqhm.1005-4979.2024.02.003 |
| [53] | 何斌, 万强琨, 周育夫, 等. BAY 11-7082对人鼻咽癌细胞增殖和凋亡的影响[J]. 齐齐哈尔医学院学报, 2020, 41(1): 1-4. |
| [54] | 周咏明, 黄炜祺, 江高峰, 等. IKKα和IKKβ信号通路在肿瘤中的作用机制及其相关药物研究进展[J]. 中国新药杂志, 2020, 29(20): 2321-2330. |
| [1] | 高腾, 赵振远, 赵梦然, 刘婕, 宋晓萌. miR-7975对口腔鳞状细胞癌恶性表型的影响[J]. 口腔医学, 2025, 45(7): 495-501. |
| [2] | 陈玥, 孙雪倩, 陈敏敏. lncRNA UCA1在口腔鳞状细胞癌中的研究进展[J]. 口腔医学, 2025, 45(4): 317-320. |
| [3] | 伊婕, 丁宇洁, 单雨菲, 顾佳麒, 孙志达. 中性粒细胞胞外诱捕网调控口腔鳞状细胞癌的发展及预后的相关研究[J]. 口腔医学, 2024, 44(7): 500-517. |
| [4] | 梁梦晴, 李志萍, 孟箭. 头颈部恶性肿瘤根治术后下肢深静脉血栓形成的风险预测模型构建[J]. 口腔医学, 2024, 44(4): 276-281. |
| [5] | 万锦波, 钱一言, 王羽立, 肖娜, 卞一峰, 杜一飞. 经侧方颈纹入路行选择性颈淋巴结清扫术的临床初探[J]. 口腔医学, 2024, 44(3): 173-176. |
| [6] | 王亚培, 罗玉春, 刘为, 刘畅, 唐婉容. EP300对口腔鳞癌细胞增殖和迁移的影响[J]. 口腔医学, 2024, 44(2): 88-93. |
| [7] | 要甜, 马宇锋. 铜死亡在口腔鳞状细胞癌治疗及预后中的研究进展[J]. 口腔医学, 2024, 44(11): 871-875. |
| [8] | 胡海艳, 高腾, 朱载瓯, 丁旭, 吴煜农, 宋晓萌. CMTM4在口腔鳞状细胞癌发生发展中的作用及机制研究[J]. 口腔医学, 2023, 43(6): 481-487. |
| [9] | 徐依萍, 黄嘉玲, 刘忠斌, 杨琨, 葛颂. 具核梭杆菌与口腔鳞状细胞癌关系的研究进展[J]. 口腔医学, 2023, 43(6): 546-551. |
| [10] | 杨月美,宋晓萌,吴煜农. Notch1P1641S突变通过PI3K/Akt通路促进口腔鳞癌增殖[J]. 口腔医学, 2023, 43(5): 393-399. |
| [11] | 肖涛, 贺一家, 朱瑶萍, 郝峰瑶, 陈艳, 王志勇. 口腔鳞癌VEGF诱导树突状细胞致免疫耐受的机制研究[J]. 口腔医学, 2023, 43(3): 204-211. |
| [12] | 肖金枝, 余伟, 张昊. 盐酸小檗碱通过调节自噬抑制口腔鳞状细胞癌增殖的研究[J]. 口腔医学, 2023, 43(10): 889-893. |
| [13] | 马萍, 程璐瑶, 金武龙, 王宁, 翟荣萍. 口腔鳞状细胞癌中NCAPD2的表达水平及生物学功能[J]. 口腔医学, 2022, 42(8): 688-693. |
| [14] | 王金鑫, 伊婕, 丁宇洁, 钟旖, 孙志达. Claudin-7在口腔鳞状细胞癌中的表达和作用研究[J]. 口腔医学, 2022, 42(7): 604-608. |
| [15] | 侯伊明, 李娜, 禹文茜, 陈磊. 组蛋白修饰在口腔鳞状细胞癌中的研究进展[J]. 口腔医学, 2022, 42(7): 650-654. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
苏公网安备32010602011670号