硫化氢在胃癌治疗中的潜在作用及研究进展

doi:10.11904/j.issn.1002-3070.2025.04.011

摘要/Abstract

摘要： 胃癌作为一种全球范围内发病率较高的恶性肿瘤,其治疗面临诸多挑战。传统的手术治疗、化疗和放疗在一定程度上可提高胃癌患者的生存率并改善生活质量,但其总体疗效仍有限,且常伴随显著的副作用。近年来,硫化氢(hydrogen sulfide,H₂S)作为一种重要的生物气体,在多种生物学过程中显示出其独特的作用,尤其是在肿瘤的发展与治疗中逐渐引起关注。研究表明,硫化氢不仅具有抗肿瘤的潜力,还可通过多种机制影响肿瘤细胞的生长、增殖和凋亡。此外,硫化氢与现有治疗手段的结合使用,可能为胃癌患者提供更为有效的治疗策略。本文旨在综述硫化氢在胃癌治疗中的潜在作用,重点探讨其抗肿瘤机制、与传统治疗手段的结合情况及安全性等方面的最新研究进展,希望为未来的胃癌治疗提供新的思路和方向,推动相关研究的深入开展,改善胃癌患者的预后与生活质量。

关键词: 硫化氢, 胃癌, 治疗策略

Abstract: Gastric cancer,as a malignant tumor with a relatively high incidence rate worldwide,faces many challenges in its treatment.Traditional surgical treatment,chemotherapy and radiotherapy can to some extent improve the survival rate and quality of life of patients with gastric cancer,but their overall efficacy is still limited and they are often accompanied by significant side effects.In recent years,hydrogen sulfide(H₂S),as an important biogas,has shown its unique role in various biological processes,especially gradually attracting attention in the development and treatment of tumors.Studies have shown that hydrogen sulfide not only has the potential to fight tumors,but also can affect the growth,proliferation and apoptosis of tumor cells through multiple mechanisms.In addition,the combined use of hydrogen sulfide with existing treatment methods may provide a more effective treatment strategy for patients with gastric cancer.This article aims to review the potential role of hydrogen sulfide in the treatment of gastric cancer,focusing on the latest research progress in its anti-tumor mechanism,combination with traditional treatment methods,and safety.It is hoped that this will provide new ideas and directions for the future treatment of gastric cancer,promote the in-depth development of related research,and improve the prognosis and quality of life of patients with gastric cancer.

Key words: Hydrogen sulfide, Gastric cancer, Therapeutic strategies

中图分类号:

代风雪, 王振飞. 硫化氢在胃癌治疗中的潜在作用及研究进展[J]. 实用肿瘤学杂志, 2025, 39(4): 330-337.

DAI Fengxue, WANG Zhenfei. Research progress on the potential role and mechanism of hydrogen sulfide in the treatment of gastric cancer[J]. Journal of Practical Oncology, 2025, 39(4): 330-337.

参考文献

1 Bray F,Laversanne M,Sung H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2024,74(3):229-263.
2 He F,Wang S,Zheng R,et al.Trends of gastric cancer burdens attributable to risk factors in China from 2000 to 2050[J].Lancet Reg Health West Pac,2024,44:101003.
3 Behar D,Boublenza L,Chabni N,et al.Retrospective epidemiological study on stomach cancer in a region of western Algeria:about 394 cases between 2011 and 2015[J].J Gastrointest Cancer,2021,52(2):706-710.
4 Kang SY,Hwang D,Shin S,et al.Potential of bioactive food components against gastric cancer:Insights into molecular mechanism and therapeutic targets[J].Cancers(Basel),2021,13(18):4502.
5 Zuhra K,Tomé CS,Forte E,et al.The multifaceted roles of sulfane sulfur species in cancer-associated processes[J].Biochim Biophys Acta Bioenerg,2021,1862(2):148338.
6 Xu Z,Zhu Y,Xie M,et al.Mackinawite nanozymes as reactive oxygen species scavengers for acute kidney injury alleviation[J].J Nanobiotechnology,2023,21(1):281.
7 Bełtowski J.Synthesis,metabolism,and signaling mechanisms of hydrogen sulfide:an overview[J].Methods Mol Biol,2019,2007:1-8.
8 Mini P,Walker SE,Grace MR,et al.Detection of aqueous and gaseous hydrogen sulfide with lanthanide-macrocycle binary complexes[J].Dalton Trans,2023,52(35):12235-12243.
9 Tabassum R,Jeong NY,Jung J.Protective effect of hydrogen sulfide on oxidative stress-induced neurodegenerative diseases[J].Neural Regen Res,2020,15(2):232-241.
10 Bhadwal SS,Verma S,Hassan S,et al.Unraveling the potential of hydrogen sulfide as a signaling molecule for plant development and environmental stress responses:a state-of-the-art review[J].Plant Physiol Biochem,2024,212:108730.
11 Kolluru GK,Shen X,Kevil CG.Reactive sulfur species:a new redox player in cardiovascular pathophysiology[J].Arterioscler Thromb Vasc Biol,2020,40(4):874-884.
12 Alsaeedi A,Welham S,Rose P,et al.The impact of drugs on hydrogen sulfide homeostasis in mammals[J].Antioxidants(Basel),2023,12(4):908.
13 Fukuto JM,Vega VS,Works C,et al.The chemical biology of hydrogen sulfide and related hydropersulfides:interactions with biologically relevant metals and metalloproteins[J].Curr Opin Chem Biol,2020,55:52-58.
14 Yang Z,Wang X,Feng J,et al.Biological functions of hydrogen sulfide in plants[J].Int J Mol Sci,2022,23(23):15107.
15 Jiang Z,Liu D,Li T,et al.Hydrogen sulfide reduces oxidative stress in Huntington′s disease via Nrf2[J].Neural Regen Res,2025,20(6):1776-1788.
16 Shen J,Zhai J,You Q,et al.Cancer-associated fibroblasts-derived VCAM1 induced by H.pylori infection facilitates tumor invasion in gastric cancer[J].Oncogene,2020,39(14):2961-2974.
17 Li X,Zhu S,Zhang T,et al.Association between oral microflora and gastrointestinal tumors(Review)[J].Oncol Rep,2021,46(2):160.
18 Li H,Guan B,Liu S,et al.PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway[J].Cell Death Dis,2023,14(3):188.
19 Chen R,Yang M,Huang W,et al.Cascades between miRNAs,lncRNAs and the NF-κB signaling pathway in gastric cancer(Review)[J].Exp Ther Med,2021,22(1):769.
20 Zeng Z,Yang B,Liao Z.Progress and prospects of immune checkpoint inhibitors in advanced gastric cancer[J].Future Oncol,2021,17(12):1553-1569.
21 Cen S,Xu H,Liu Z,et al.Immune microenvironment characteristics and their implications for immune checkpoint inhibitor efficacy in HER2-overexpressing gastric cancer[J].Clin Exp Immunol,2022,207(3):318-328.
22 Zeng Z,Zhu Q.Progress and prospects of biomarker-based targeted therapy and immune checkpoint inhibitors in advanced gastric cancer[J].Front Oncol,2024,14:1382183.
23 Li J,Zhang H,Bei S,et al.Disruption of wnt/β-catenin pathway elevates the sensitivity of gastric cancer cells to PD-1 antibody[J].Curr Mol Pharmacol,2022,15(3):557-569.
24 Kumagai S,Togashi Y,Sakai C,et al.An oncogenic alteration creates a microenvironment that promotes tumor progression by conferring a metabolic advantage to regulatory T cells[J].Immunity,2020,53(1):187-203.e188.
25 Bagheri M,Akrami H.Studying the non-coding RNA expression and its role in drug resistance mechanisms of gastric cancer[J].Pathol Res Pract,2025,265:155742.
26 Cui MY,Yi X,Zhu DX,et al.The role of lipid metabolism in gastric cancer[J].Front Oncol,2022,12:916661.
27 Huang Y,Liang L,Zhao YX,et al.RUNX2 reverses p53-induced chemotherapy resistance in gastric cancer[J].Pharmgenomics Pers Med,2023,16:253-261.
28 Wang R,Tao B,Fan Q,et al.Fatty-acid receptor CD36 functions as a hydrogen sulfide-targeted receptor with its Cys333-Cys272 disulfide bond serving as a specific molecular switch to accelerate gastric cancer metastasis[J].EBioMedicine,2019,45:108-123.
29 Kawahara Y,Hirashita Y,Tamura C,et al.Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells[J].Helicobacter,2020,25(5):e12732.
30 Ma W,Zhang X,Zhuang L.Exogenous hydrogen sulfide induces A375 melanoma cell apoptosis through overactivation of the unfolded protein response[J].Clin Cosmet Investig Dermatol,2023,16:1641-1651.
31 Wang H,Li X,Zhu Z,et al.Hydrogen sulfide promotes lipopolysaccharide-induced apoptosis of osteoblasts by inhibiting the Akt/NF-κB signaling pathway[J].Biochem Biophys Res Commun,2020,524(4):832-838.
32 Padmanabhan N,Kyon HK,Boot A,et al.Author correction:highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation[J].Genome Biol,2021,22(1):181.
33 Ye F,Li X,Sun K,et al.Inhibition of endogenous hydrogen sulfide biosynthesis enhances the anti-cancer effect of 3,3′-diindolylmethane in human gastric cancer cells[J].Life Sci,2020,261:118348.
34 Cui Q,Yang Y,Ji N,et al.Gaseous signaling molecules and their application in resistant cancer treatment:from invisible to visible[J].Future Med Chem,2019,11(4):323-336.
35 Tian L,Pei R,Zhang X,et al.Tumor cell-specific and lipase-responsive delivery of hydrogen sulfide for sensitizing chemotherapy of pancreatic cancer[J].Front Bioeng Biotechnol,2022,10:934151.
36 Liang X,Kurboniyon MS,Zou Y,et al.GSH-triggered/photothermal-enhanced H(2)S signaling molecule release for gas therapy[J].Pharmaceutics,2023,15(10):2443.
37 Li J,Xie L,Sang W,et al.A metal-phenolic nanosensitizer performs hydrogen sulfide-reprogrammed oxygen metabolism for cancer radiotherapy intensification and immunogenicity[J].Angew Chem Int Ed Engl,2022,61(18):e202200830.
38 Liu C,Zhang Y,Sun W,et al.H(2)S-activated fluorescent probe enables dual-channel fluorescence tracking of drug release in tumor cells[J].Bioorg Chem,2023,135:106498.
39 Yang XY,Luo ZQ,Fang D,et al.Hollow copper sulfide nanocubes loaded with pt(IV)complexes for cancer multimodal therapy[J].Langmuir,2024,40(43):22875-22886.
40 Wang K,Li Y,Wang X,et al.Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation[J].Nat Commun,2023,14(1):2950.
41 Li M,Liu Y,Zhang Y,et al.Sono-activatable semiconducting polymer nanoreshapers multiply remodel tumor microenvironment for potent immunotherapy of orthotopic pancreatic cancer[J].Adv Sci(Weinh),2023,10(35):e2305150.
42 Sun M,Wang T,Zhu Y,et al.Gas immnuo-nanomedicines fight cancers[J].Biomed Pharmacother,2024,180:117595.
43 Paul BD,Snyder SH,Kashfi K.Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics[J].Redox Biol,2021,38:101772.
44 Zhang G,Wang G,Zhou Y,et al.Simultaneous use of nitrate and calcium peroxide to control sulfide and greenhouse gas emission in sewers[J].Sci Total Environ,2023,855:158913.
45 Al-Jassim M,Frazier T,Wood E.Emergency management and HAZMAT mitigation:Strategic planning for new developments[J].J Emerg Manag,2023,20(8):39-57.
46 Mahato SK,Barman P,Badirujjaman M,et al.Cysteine-responsive prodrug of the anti-cancer drug amonafide:fluorogenic adjuvant drug delivery with hydrogen sulfide(H2S)[J].Chem Commun(Camb),2023,59(32):4802-4805.
47 Yuan T,Hashimoto K,Tazaki A,et al.Potential application of a hydrotalcite-like compound for reduction of toxicity to aquatic organisms via rapid and efficient removal of hydrogen sulfide[J].J Environ Manage,2022,321:115861.
48 Pan Y,Huang Z,Zheng D,et al.Interface engineering of sandwich SiO(2)@α-Fe(2)O(3)@COF core-shell S-scheme heterojunctions for efficient photocatalytic oxidation of gas-phase H2S[J].J Colloid Interface Sci,2023,644:19-28.
49 Park J,Kang T,Heo Y,et al.Evaluation of short-term exposure levels on ammonia and hydrogen sulfide during manure-handling processes at livestock farms[J].Saf Health Work,2020,11(1):109-117.
50 Santos SL,Holz C,Milleman K,et al.Effectiveness of a combination of laccase and green coffee extract on oral malodor:a comparative,randomized,controlled,evaluator-blind,parallel-group trial[J].J Breath Res,2024,19(1):10.
51 Yu JG,Li N,Wang Z,et al.Dual modulating effects of hydrogen sulfide on gastrointestinal tract and efficacy-toxicity transformation of hydrogen sulfide-mediated drugs[J].Zhongguo Zhong Yao Za Zhi,2022,47(15):3986-3993.
52 Wu D,Hu Q,Ma F,et al.Vasorelaxant effect of a new hydrogen sulfide-nitric oxide conjugated donor in isolated rat aortic rings through cGMP pathway[J].Oxid Med Cell Longev,2016,2016:7075682.
53 Li C,Hu M,Wang Y,et al.Hydrogen sulfide preconditioning protects against myocardial ischemia/reperfusion injury in rats through inhibition of endo/sarcoplasmic reticulum stress[J].Int J Clin Exp Pathol,2015,8(7):7740-7751.
54 Gao X,Li HN,Liu PJ,et al.Synthesis of sinomenine derivatives with potential anti-leukemia activity[J].J Asian Nat Prod Res,2024:1-17.
55 Pandey T,Pandey V.Advancements in increasing efficiency of hydrogen sulfide in therapeutics:strategies for targeted delivery as prodrugs[J].Nitric Oxide,2024,152:1-10.
56 Özatik FY,Özatik O,Tekşen Y,et al.Dose-dependent effect of hydrogen sulfide in cyclophosphamide-induced hepatotoxicity in rats[J].Turk J Gastroenterol,2023,34(6):626-634.
57 Hooshmand S,Kassanos P,Keshavarz M,et al.Wearable nano-based gas sensors for environmental monitoring and encountered challenges in optimization[J].Sensors(Basel),2023,23(20):8648.
58 Polhemus DJ,Li Z,Pattillo CB,et al.A novel hydrogen sulfide prodrug,SG1002,promotes hydrogen sulfide and nitric oxide bioavailability in heart failure patients[J].Cardiovasc Ther,2015,33(4):216-226.
59 Lancia M,Panata L,Tondi V,et al.A fatal work-related poisoning by hydrogen sulfide:report on a case[J].Am J Forensic Med Pathol,2013,34(4):315-317.
60 Vales A,Coyle C,Plehhova K,et al.Randomised clinical trial:the use of alginates during preinvestigation proton pump inhibitor wash-out and their impact on compliance and symptom burden[J].BMJ Open Gastroenterol,2023,10(1):e001026.
61 Stoppa G,Nuvolone D,Petri D,et al.Exposure to low levels of hydrogen sulphide and its impact on chronic obstructive pulmonary disease and lung function in the geothermal area of mt.amiata in italy:the cross-sectional inVETTA study[J].PLoS One,2023,18(11):e0293619.
62 Zong Y,Tanaka M,Muramatsu M,et al.D-amino acid oxidase(DAO)rare genetic missense variant p.pro103leu and gastric cancer[J].Mol Clin Oncol,2021,14(3):58.
63 Szponarski M,Gademann K.Antibody recognition of cancer cells via glycan surface engineering[J].Chembiochem,2022,23(15):e202200125.
64 Tian Q,Wang X,Song S,et al.Engineering of an endogenous hydrogen sulfide responsive smart agent for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon cancer[J].J Adv Res,2022,41:159-168.
65 Zhao Y,Steiger AK,Pluth MD.Cyclic sulfenyl thiocarbamates release carbonyl sulfide and hydrogen sulfide independently in thiol-promoted pathways[J].J Am Chem Soc,2019,141(34):13610-13618.
66 Liu J,Tian R,Sun C,et al.Microbial metabolites are involved in tumorigenesis and development by regulating immune responses[J].Front Immunol,2023,14:1290414.
67 Wang Z,Wang Y.Hydrogen sulfide:a rising star for cancer treatment[J].Med Gas Res,2025,15(1):114-116.
68 Bazzal AA,Hoteit BH,Chokor M,et al.Potential therapeutic applications of medical gases in cancer treatment[J].Med Gas Res,2025,15(2):309-317.
69 Majumder A.Targeting homocysteine and hydrogen sulfide balance as future therapeutics in cancer treatment[J].Antioxidants(Basel),2023,12(8):1520.

[1]	吴小帆, 李琳. 卵巢癌中紫杉醇耐药性研究进展[J]. 实用肿瘤学杂志, 2025, 39(4): 343-347.
[2]	陈丽娟, 马欣欣, 高光强, 田虹, 刘家仁. 二氢猕猴桃内酯抑制胃癌细胞增殖的作用机制研究[J]. 实用肿瘤学杂志, 2025, 39(2): 91-98.
[3]	马铭, 王婉莹, 阮玉莉, 刘超, 张艳桥, 马志刚. 全身炎症免疫营养评分判断晚期胃癌免疫治疗预后的价值分析[J]. 实用肿瘤学杂志, 2025, 39(1): 39-48.
[4]	孔虹倩, 董娟, 文洪梅, 邵英, 成会荣, 余秋丽. 云南省肿瘤登记地区2020年胃癌发病和死亡情况及2012—2020年趋势分析[J]. 实用肿瘤学杂志, 2024, 38(6): 372-376.
[5]	赵倩雯, 佘欣, 耿利军, 彭丹莉, 刘姗姗. 1990—2021年中国胃癌发病趋势的年龄-时期-队列[J]. 实用肿瘤学杂志, 2024, 38(5): 289-294.
[6]	廖俊, 李春峰, 薛英威, 祖洪亮. 乳酸脱氢酶在胃癌诊治中的研究进展[J]. 实用肿瘤学杂志, 2024, 38(3): 200-206.
[7]	杨鹏, 罗金梅, 罗萍, 谢小波. 基于免疫细胞浸润的免疫评分模型预测早期胃癌免疫治疗效果及预后[J]. 实用肿瘤学杂志, 2024, 38(2): 121-130.
[8]	高超峰, 赵泽坤, 魏丰贤, 孙元, 周志明, 徐小东. 胃癌围术期营养管理的研究进展[J]. 实用肿瘤学杂志, 2023, 37(6): 519-523.
[9]	付鑫雅, 胡灵丹, 张志坚, 马秀梅. HPA通过上调MCP-1/CCR2促进胃癌发生侵袭和转移[J]. 实用肿瘤学杂志, 2023, 37(4): 329-336.
[10]	李娟, 刘家仁. 胃癌免疫治疗的研究现状及进展[J]. 实用肿瘤学杂志, 2023, 37(4): 372-376.
[11]	周海茸, 王巍巍, 王琛琛, 洪忻. 2007—2019年南京市胃癌死亡率及早死寿命损失年变化趋势分析[J]. 实用肿瘤学杂志, 2023, 37(2): 102-106.
[12]	明成, 武云. Wnt信号通路及其抑制剂在胃癌中的研究进展[J]. 实用肿瘤学杂志, 2023, 37(2): 190-194.
[13]	杨菊, 刘芹, 刘宝瑞, 魏嘉. 胃癌相关癌睾抗原筛选与免疫浸润分析[J]. 实用肿瘤学杂志, 2022, 36(6): 495-501.
[14]	徐伟, 刘海鹏, 汪文杰, 王舟, 李元元, 沈亦敏, 陈晓. 胃癌术后胆囊结石形成的危险因素及预防措施的研究进展[J]. 实用肿瘤学杂志, 2022, 36(6): 561-565.
[15]	赵雅茹, 武云. 胃癌常见生物标记物及相应靶向治疗的研究进展[J]. 实用肿瘤学杂志, 2022, 36(5): 483-488.