霍乱毒素抗肿瘤作用的研究进展

doi:10.11958/20253460

天津医药 ›› 2026, Vol. 54 ›› Issue (4): 438-443.doi: 10.11958/20253460

霍乱毒素抗肿瘤作用的研究进展

刘家妮¹(), 苏帅², 张爱婷², 徐昕², 王邦茂²^△()

¹ 北京大学国际医院消化内科（邮编102200）
² 天津医科大学总医院消化内科

收稿日期:2025-12-01 修回日期:2025-12-29 出版日期:2026-04-15 发布日期:2026-04-14
通讯作者: ^△E-mail：mwang02@tmu.edu.cn
作者简介:刘家妮（1997），女，医师，主要从事消化系统肿瘤方面研究。E-mail：LJN1997@tmu.edu.cn
基金资助:
国家自然科学基金资助项目(82170558);国家自然科学基金资助项目(82370545)

Advances in the anti-tumor effects of cholera toxin

LIU Jiani¹(), SU Shuai², ZHANG Aiting², XU Xin², WANG Bangmao²^△()

¹ Department of Gastroenterology, Peking University International Hospital, Beijing 102200, China
² Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital

Received:2025-12-01 Revised:2025-12-29 Published:2026-04-15 Online:2026-04-14
Contact: ^△E-mail：mwang02@tmu.edu.cn

刘家妮, 苏帅, 张爱婷, 徐昕, 王邦茂. 霍乱毒素抗肿瘤作用的研究进展[J]. 天津医药, 2026, 54(4): 438-443.

LIU Jiani, SU Shuai, ZHANG Aiting, XU Xin, WANG Bangmao. Advances in the anti-tumor effects of cholera toxin[J]. Tianjin Medical Journal, 2026, 54(4): 438-443.

摘要/Abstract

摘要：

霍乱毒素是霍乱弧菌分泌的一种AB5型毒素，具有免疫调节能力。霍乱毒素在抗肿瘤方面具有一定作用，其不但可通过抑制生长因子信号或触发细胞凋亡来抑制细胞增殖，还可作为一种免疫调节剂，通过介导炎症反应、调节免疫系统来抑制肿瘤的发生发展。此外，霍乱毒素还可以通过辅助靶向药物运输和作为疫苗佐剂发挥间接抗肿瘤作用。该文就霍乱毒素在肿瘤中的作用予以综述，为肿瘤的预防及治疗提供新思路。

关键词: 霍乱毒素, 肿瘤, 佐剂, 免疫, 疫苗, 细胞增殖, 免疫调节

Abstract:

Cholera toxin is an AB5-type toxin secreted by vibrio cholerae and has the ability to regulate immunity. Research has found that cholera toxin has potential anti-cancer effects. It not only inhibits cell proliferation by suppressing growth factor signaling or triggering apoptosis, but also acts as an immunomodulator by mediating inflammatory responses and regulating the immune system to inhibit tumor occurrence and development. Additionally, cholera toxin can also indirectly exert anti-tumor effects by assisting in targeted drug delivery and serving as an adjuvant in vaccines. This article reviews the role of cholera toxin in tumors, providing new ideas for cancer prevention and treatment.

Key words: cholera toxin, neoplasms, adjuvants, immunologic, vaccines, cell proliferation, immunomodulation

中图分类号:

R730.1

图/表 1

参考文献 39

[1]	张希, 杨雷, 刘硕, 等. 2022年全球恶性肿瘤统计报告解读[J]. 中华肿瘤杂志, 2024, 46(7):710-721.
	ZHANG X, YANG L, LIU S, et al. Interpretation on the report of global cancer statistics 2022[J]. Chin J Oncol, 2024, 46(7):710-721. doi:10.3760/cma.j.cn112152-20240416-00152.
[2]	HANAHAN D. Hallmarks of cancer:New dimensions[J]. Cancer Discov, 2022, 12(1):31-46. doi:10.1158/2159-8290.CD-21-1059.
[3]	张兴隆, 何红梅, 张静, 等. 人工胸水技术联合射频消融术对膈顶部肝癌患者的临床疗效[J]. 天津医药, 2025, 53(8):856-859.
	ZHANG X L, HE H M, ZHANG J, et al. The clinical efficacy of artificial pleural effusion combined with radiofrequency ablation in patients with phrenic top liver cancer[J]. Tianjin Med J, 2025, 53(8):856-859. doi:10.11958/20250709.
[4]	SHARMA P C, SHARMA D, SHARMA A, et al. Recent advances in microbial toxin-related strategies to combat cancer[J]. Semin Cancer Biol, 2022, 86(Pt 3):753-768. doi:10.1016/j.semcancer.2021.07.007.
[5]	CHOWDHURY F, ROSS A G, ISLAM M T, et al. Diagnosis,management,and future control of cholera[J]. Clin Microbiol Rev, 2022, 35(3):e0021121. doi:10.1128/cmr.00211-21.
[6]	VERJAN GARCIA N, SANTISTEBAN CELIS I C, DENT M, et al. Characterization and utility of two monoclonal antibodies to cholera toxin B subunit[J]. Sci Rep, 2023, 13(1):4305. doi:10.1038/s41598-023-30834-2.
[7]	KAUR G, VIALLET J, LABORDA J, et al. Growth inhibition by cholera toxin of human lung carcinoma cell lines:correlation with GM1 ganglioside expression[J]. Cancer Res, 1992, 52(12):3340-3346.
[8]	LI Y, YIN W, WANG X, et al. Cholera toxin induces malignant glioma cell differentiation via the PKA/CREB pathway[J]. Proc Natl Acad Sci U S A, 2007, 104(33):13438-13443. doi:10.1073/pnas.0701990104.
[9]	SHU M, ZHOU Y, ZHU W, et al. Activation of a pro-survival pathway IL-6/JAK2/STAT3 contributes to glial fibrillary acidic protein induction during the cholera toxin-induced differentiation of C6 malignant glioma cells[J]. Mol Oncol, 2011, 5(3):265-272. doi:10.1016/j.molonc.2011.03.003.
[10]	XIA Q, DENG A M, WU S S, et al. Cholera toxin inhibits human hepatocarcinoma cell proliferation in vitro via suppressing ATX/LPA axis[J]. Acta Pharmacol Sin, 2011, 32(8):1055-1062. doi:10.1038/aps.2011.31.
[11]	ZHENG X, OU Y, SHU M, et al. Cholera toxin,a typical protein kinase A activator,induces G1 phase growth arrest in human bladder transitional cell carcinoma cells via inhibiting the c-Raf/MEK/ERK signaling pathway[J]. Mol Med Rep, 2014, 9(5):1773-1779. doi:10.3892/mmr.2014.2054.
[12]	MEUNIER M, SPILLMANN A, ROUSSEAUX C, et al. An oral cholera vaccine in the prevention and/or treatment of inflammatory bowel disease[J]. PLoS One, 2023, 18(8):e0283489. doi:10.1371/journal.pone.0283489.
[13]	DOULBERIS M, ANGELOPOULOU K, KALDRYMIDOU E, et al. Cholera-toxin suppresses carcinogenesis in a mouse model of inflammation-driven sporadic colon cancer[J]. Carcinogenesis, 2015, 36(2):280-290. doi:10.1093/carcin/bgu325.
[14]	STRATMANN T. Cholera toxin subunit B as adjuvant--an accelerator in protective immunity and a break in autoimmunity[J]. Vaccines(Basel), 2015, 3(3):579-596. doi:10.3390/vaccines3030579.
[15]	ISOMURA I, YASUDA Y, TSUJIMURA K, et al. Recombinant cholera toxin B subunit activates dendritic cells and enhances antitumor immunity[J]. Microbiol Immunol, 2005, 49(1):79-87. doi:10.1111/j.1348-0421.2005.tb03632.x.
[16]	OCHANDO J, MULDER W, MADSEN J C, et al. Trained immunity-basic concepts and contributions to immunopathology[J]. Nat Rev Nephrol, 2023, 19(1):23-37. doi:10.1038/s41581-022-00633-5.
[17]	TEPALE-SEGURA A, GAJÓN J A, MUÑOZ-CRUZ S, et al. The cholera toxin B subunit induces trained immunity in dendritic cells and promotes CD8 T cell antitumor immunity[J]. Front Immunol, 2024, 15:1362289. doi:10.3389/fimmu.2024.1362289.
[18]	BALDAUF K J, ROYAL J M, KOUOKAM J C, et al. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon[J]. Mucosal Immunol, 2017, 10(4):887-900. doi:10.1038/mi.2016.95.
[19]	GUAN J, QIAN J, ZHAN C. Preparation of cholera toxin subunit B functionalized nanoparticles for targeted therapy of glioblastoma[J]. Methods Mol Biol, 2020,2059:207-212. doi:10.1007/978-1-4939-9798-5_10.
[20]	GUAN J, ZHANG Z, HU X, et al. Cholera toxin subunit B enabled multifunctional glioma-targeted drug delivery[J]. Adv Healthc Mater, 2017, 6(23):1700709. doi:10.1002/adhm.201700709.
[21]	ZHANG X, TANG W, WEN H, et al. Evaluation of CTB-sLip for targeting lung metastasis of colorectal cancer[J]. Pharmaceutics, 2022, 14(4):868. doi:10.3390/pharmaceutics14040868.
[22]	LIN Z, TANG Y, CHEN Z, et al. Soluble CD80 oral delivery by recombinant Lactococcus suppresses tumor growth by enhancing antitumor immunity[J]. Bioeng Transl Med, 2023, 8(4):e10533. doi:10.1002/btm2.10533.
[23]	KACZMAREK M, POZNAŃSKA J, FECHNER F, et al. Cancer vaccine therapeutics:limitations and effectiveness-A literature review[J]. Cells, 2023, 12(17):2159. doi:10.3390/cells12172159.
[24]	ZHAO T, CAI Y, JIANG Y, et al. Vaccine adjuvants:mechanisms and platforms[J]. Signal Transduct Target Ther, 2023, 8(1):283. doi:10.1038/s41392-023-01557-7.
[25]	ZHOU Z, DONG H, HUANG Y, et al. Recombinant Bacillus subtilis spores expressing cholera toxin B subunit and Helicobacter pylori urease B confer protection against H. pylori in mice[J]. J Med Microbiol, 2017, 66(1):83-89. doi:10.1099/jmm.0.000404.
[26]	LV X, YANG J, SONG H, et al. Therapeutic efficacy of the multi-epitope vaccine CTB-UE against Helicobacter pylori infection in a Mongolian gerbil model and its microRNA-155-associated immuno-protective mechanism[J]. Vaccine, 2014, 32(41):5343-5352. doi:10.1016/j.vaccine.2014.07.041.
[27]	LIN D, HE H, SUN J, et al. Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses[J]. Vaccine, 2021, 39(11):1609-1620. doi:10.1016/j.vaccine.2021.02.002.
[28]	HE X, FAN K, GONG H, et al. Mechanism study of cross presentation of exogenous antigen induced by cholera toxin-like chimeric protein[J]. Vaccine, 2024, 42(7):1549-1560. doi:10.1016/j.vaccine.2024.01.075.
[29]	AFALONIATI H, AINDELIS G, SPYRIDOPOULOU K, et al. Peri-weaning cholera toxin consumption suppresses chemically-induced carcinogenesis in mice[J]. Int J Cancer, 2024, 154(6):1097-1110. doi:10.1002/ijc.34816.
[30]	SIT B, FAKOYA B, WALDOR M K. Emerging concepts in cholera vaccine design[J]. Annu Rev Microbiol, 2022, 76:681-702. doi:10.1146/annurev-micro-041320-033201.
[31]	SONG K R, LIM J K, PARK S E, et al. Oral cholera vaccine efficacy and effectiveness[J]. Vaccines(Basel), 2021, 9(12):1482. doi:10.3390/vaccines9121482.
[32]	MONTERO D A, VIDAL R M, VELASCO J, et al. Vibrio cholerae,classification,pathogenesis,immune response,and trends in vaccine development[J]. Front Med(Lausanne), 2023, 10:1155751. doi:10.3389/fmed.2023.1155751.
[33]	JI J, SUNDQUIST J, SUNDQUIST K. Cholera vaccine use is associated with a reduced risk of death in patients with colorectal cancer:A population-based study[J]. Gastroenterology, 2018, 154(1):86-92.e1. doi:10.1053/j.gastro.2017.09.009.
[34]	ZHENG G, SUNDQUIST J, SUNDQUIST K, et al. Association of post-diagnostic use of cholera vaccine with survival outcome in breast cancer patients[J]. Br J Cancer, 2021, 124(2):506-512. doi:10.1038/s41416-020-01108-9.
[35]	JI J, SUNDQUIST J, SUNDQUIST K. Association between post-diagnostic use of cholera vaccine and risk of death in prostate cancer patients[J]. Nat Commun, 2018, 9(1):2367. doi:10.1038/s41467-018-04814-4.
[36]	SAIF-UR-RAHMAN K M, MAMUN R, HASAN M, et al. Oral killed cholera vaccines for preventing cholera[J]. Cochrane Database Syst Rev, 2024, 1(1):CD014573. doi:10.1002/14651858.CD014573.
[37]	COLLINS J P, RYAN E T, WONG K K, et al. Cholera vaccine:Recommendations of the Advisory Committee on Immunization Practices,2022[J]. MMWR Recomm Rep, 2022, 71(2):1-8. doi:10.15585/mmwr.rr7102a1.
[38]	EL HAYEK P, BOUERI M, NASR L, et al. Cholera infection risks and cholera vaccine safety in pregnancy[J]. Infect Dis Obstet Gynecol, 2023, 2023:4563797. doi:10.1155/2023/4563797.
[39]	YUKI Y, NOJIMA M, KASHIMA K, et al. Oral MucoRice-CTB vaccine is safe and immunogenic in healthy US adults[J]. Vaccine, 2022, 40(24):3372-3379. doi:10.1016/j.vaccine.2022.04.051.

霍乱毒素抗肿瘤作用的研究进展

Advances in the anti-tumor effects of cholera toxin

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 1

参考文献 39

相关文章 15

编辑推荐

Metrics

本文评价

[1]	钱永, 陈沐秀, 郑爽. COX-2在口腔鳞状细胞癌增殖与侵袭中的作用研究[J]. 天津医药, 2026, 54(4): 352-357.
[2]	陈一铭, 戈超, 徐姝琪, 孙威, 戴颖, 徐选福. CYP1B1和PSMD14在结直肠癌中的表达及其对预后的影响[J]. 天津医药, 2026, 54(4): 412-416.
[3]	孙广海, 刘春林, 韩鸿雁, 徐汉军, 曹春晖. 维迪西妥单抗联合特瑞普利单抗治疗肌层浸润性膀胱癌的疗效观察[J]. 天津医药, 2026, 54(4): 429-433.
[4]	石岩, 张鹏, 张园, 王晨光, 续文栋, 陈渊. 胸壁巨大肉瘤切除伴碳纤维人工肋骨重建和背阔肌肌皮瓣移植1例[J]. 天津医药, 2026, 54(4): 434-437.
[5]	姜天佑, 李敏, 孙碧文, 李越洋, 邢丽静, 田晨. Let-7b诱导白血病相关巨噬细胞复极抑制AML的发展[J]. 天津医药, 2026, 54(3): 225-231.
[6]	杨晓芳, 贾新燕, 丰文君. miR-181a-5p通过HMGB1/NF-κB信号通路调控狼疮性肾炎小鼠肾小球系膜细胞增殖和凋亡[J]. 天津医药, 2026, 54(3): 232-237.
[7]	宋铁军, 林宁宁, 杨悦漪, 王亚斐. 光动力疗法联合超分子水杨酸治疗中重度痤疮患者的疗效分析[J]. 天津医药, 2026, 54(3): 254-258.
[8]	赵丽, 马秀丽, 刘毅, 朱毅. 全麻下腹腔镜胃癌根治术后谵妄发生的危险因素分析[J]. 天津医药, 2026, 54(3): 259-264.
[9]	李明, 金建华, 吴建亭, 王君辉, 许俊. 个性化腰垫与体膜联合固定对宫颈癌放疗患者摆位精度及稳定性的影响[J]. 天津医药, 2026, 54(3): 299-302.
[10]	苏雅, 张东伟, 宇明慧, 王春花, 吴月月. 复方苦参注射液联合靶向和免疫治疗对晚期肝癌的疗效观察[J]. 天津医药, 2026, 54(3): 324-328.
[11]	于洋, 谷梦青. 女性生殖健康调控机制与研究进展[J]. 天津医药, 2026, 54(2): 113-116.
[12]	王喆, 邱林, 马贲. 番茄来源胞外囊泡样颗粒对口腔鳞状细胞癌的作用效果研究[J]. 天津医药, 2026, 54(2): 145-150.
[13]	冯昊, 郭晓双, 任晓静, 李明. 吴茱萸汤联合甲磺酸多拉司琼治疗化疗所致呕吐的疗效分析[J]. 天津医药, 2026, 54(2): 201-205.
[14]	张鑫, 赵佳媛, 毕哲慧, 刘焱, 陈青宇. 稀土元素在氧化锆口腔修复材料中的应用与展望[J]. 天津医药, 2026, 54(2): 220-224.
[15]	庄瑞玲, 杨杰, 陈艳欣, 张雲. 基于转录组与代谢组学联合分析谷氨酰胺合成酶在慢性髓系白血病耐药中的作用机制[J]. 天津医药, 2026, 54(1): 1-7.