微生态调节剂在肿瘤治疗中的应用
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摘要
肿瘤的治疗方法包括手术治疗、化学治疗、放射治疗、靶向治疗、免疫治疗等。但是药物副反应、疾病耐药和肿瘤复发是目前面临的困难。近年来,微生物与肿瘤相互作用的研究成为热点。越来越多的研究表明,可以通过调节微生态来对抗肿瘤,提高肿瘤治疗的疗效,减小治疗的副作用,从而进一步提高肿瘤患者的生活质量。本文就微生态调节剂应用于治疗肿瘤作一综述,我们回顾了有关益生菌在肿瘤治疗中的应用,此外,我们讨论益生菌、益生元、合生元、微生物代谢物和抗生素与化疗及免疫治疗共同应用的益处。
The treatment methods of tumors include surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy and so on. However, side effects of drugs, drug resistance, and tumor recurrence are currently the challenges we are facing. In recent years, the research on the interaction between microorganisms and tumors has become a hot topic. More and more studies have shown that regulation of microbiome can fight tumors, improve the curative effect, reduce the side effects of treatment and then improve the quality of life(QOL) of tumor patients. This article reviews the application of microbiome modulators in the treatment of tumors. We reviewed the application of probiotics in tumor treatment, and discussed the benefits of probiotics, prebiotics, synbiotics, microbial metabolites and antibiotics combined with chemotherapy and immunotherapy.
The treatment methods of tumors include surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy and so on. However, side effects of drugs, drug resistance, and tumor recurrence are currently the challenges we are facing. In recent years, the research on the interaction between microorganisms and tumors has become a hot topic. More and more studies have shown that regulation of microbiome can fight tumors, improve the curative effect, reduce the side effects of treatment and then improve the quality of life(QOL) of tumor patients. This article reviews the application of microbiome modulators in the treatment of tumors. We reviewed the application of probiotics in tumor treatment, and discussed the benefits of probiotics, prebiotics, synbiotics, microbial metabolites and antibiotics combined with chemotherapy and immunotherapy.
引文
[1] WANG Hongyang.Development of tumor biomarkers in the age of precision medicine[J].J Shandong Univ (Health Sci),2018,56(10):1-2.(in Chinese) 王红阳.精准医疗时代的肿瘤生物标志物发展[J].山东大学学报(医学版),2018,56(10):1-2.
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[47] Wallace BD,Wang H,Lane KT,et al.Alleviating cancer drug toxicity by inhibiting a bacterial enzyme [J].Science,2010,330(6005):831-835.
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[2] Doorakkers E,Lagergren J,Engstrand L,et al.Eradication of Helicobacter pylori and gastric cancer:a systematic review and meta-analysis of cohort studies[J].J Natl Cancer Inst,2016,108(9).pii:djw132.
[3] Sato F,Meltzer SJ.CpG island hypermethylation in progression of esophageal and gastric cancer [J].Cancer,2006,106(3):483-493.
[4] De Witte C,Schulz C,Smet A,et al.Other Helicobacters and gastric microbiota[J].Helicobacter,2016,21(Suppl 1):62-68.
[5] Nasrollahzadeh D,Malekzadeh R,Ploner A,et al.Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia[J].Sci Rep,2015,5:8820.
[6] Ginsburg I.Role of lipoteichoic acid in infection and inflammation[J].Lancet Infect Dis,2002,2(3):171-179.
[7] Chiu WT,LIN YL,CHOU CW,et al.Propofol inhibits lipoteichoic acid-induced iNOS gene expression in macrophages possibly through downregulation of toll-like receptor 2-mediated activation of Raf-MEK1/ 2-ERK1/ 2-IKK-NFκB[J].Chem Biol Interact,2009,181(3):430-439.
[8] Kuo WT,Lee TC,Yang HY,et al.LPS receptor subunits have antagonistic roles in epithelial apoptosis and colonic carcinogenesis[J].Cell Death Differ,2015,22(10):1590-1604.
[9] Wu S,Rhee KJ,Albesiano E,et al.A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses[J].Nat Med,2009,15(9):1016-1022.
[10] Cao HJ,Fang Y,Zhang X,et al.Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue[J].World J Gastroenterol,2005,11(6):903-907.
[11] Fox JG,Feng Y,Theve EJ,et al.Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens[J].Gut,2010,59(1):88-97.
[12] Grat M,Wronka Km,Krasnod?bski M,et al.Profile of gut microbiota associated with the presence of hepatocellular cancer in patients with liver cirrhosis[J].Transplant Proc,2016,48(5):1687-1691.
[13] Zhou D,Wang JD,Weng MZ,et al.Infections of Helicobacter spp.in the biliary system are associated with biliary tract cancer:a meta-analysis[J].Eur J Gastroenterol Hepatol,2013,25(4):447-454.
[14] Gui QF,Lu HF,Zhang CX,et al.Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model[J].Genet Mol Res,2015,14(2):5642-5651.
[15] Gogineni VK,Morrow LE,Malesker MA.Probiotics:mechanisms of action and clinical applications[J].J Prob Healty,2013,1(1):101.
[16] Pandey KR,Naik SR,Vakil BV.Probiotics,prebiotics and synbiotics- a review[J].J Food Sci Technol,2015,52(12):7577-7587.
[17] Serban DE.Gastrointestinal cancers:influence of gut microbiota,probiotics and prebiotics[J].Cancer Lett,2014,345(2):258-270.
[18] McLoughlin RF,BERTHON BS,JENSEN ME,et al.Short-chain fatty acids,prebiotics,synbiotics,and systemic inflammation:a systematic review and meta-analysis[J].Am J Clin Nutr,2017,106(3):930-945.
[19] Zitvogel L,Galluzzi L,Viaud S,et al.Cancer and the gut microbiota:an unexpected link[J].Sci Transl Med,2015,7(271):271ps1.
[20] Patel RM,Denning PW.Therapeutic use of prebiotics,probiotics,and postbiotics to prevent necrotizing enterocolitis:what is the current evidence?[J].Clin Perinatol,2013,40(1):11-25.
[21] Tsilingiri K,Rescigno M.Postbiotics:what else?[J].Benef Microbes,2013,4(1):101-107.
[22] Kuugbee ED,Shang X,Gamallat Y,et al.Structural change in microbiota by a probiotic cocktail enhances the gut barrier and reduces cancer via TLR2 signaling in a rat model of colon cancer[J].Dig Dis Sci,2016,61(10):2908-2920.
[23] Bultman SJ.Emerging roles of the microbiome in cancer[J].Carcinogenesis,2014,35(2):249-255.
[24] Singh N,Gurav A,Sivaprakasam S,et al.Activation of Gpr109a,receptor for niacin and the commensal metabolite butyrate,suppresses colonic inflammation and carcinogenesis[J].Immunity,2014,40(1):128-139.
[25] Donohoe DR,Holley D,Collins LB,et al.A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner[J].Cancer Discov,2014,4(12):1387-1397.
[26] Aghazadeh Z,Pouralibaba F,Yari Khosroushahi A.The prophylactic effect of Acetobacter syzygii probiotic species against squamous cell carcinoma[J].J Dent Res Dent Clin Dent Prospects,2017,11(4):208-214.
[27] Chen ZY,Hsieh YM,Huang CC,et al.Inhibitory effects of probiotic Lactobacillus on the growth of human colonic carcinoma cell line HT-29[J].Molecules,2017,22(1).pii:E107.
[28] Nozari S,Mohammadzadeh M,Faridvand Y,et al.The study of extracellular protein fractions of probiotic candidate bacteria on cancerous cell line[J].Arch Iran Med 2016,19(11):779-785.
[29] Kadirareddy RH,Vemuri SG,Palempalli UMD.Probiotic conjugated linoleic acid mediated apoptosis in breast cancer cells by downregulation of NFκB[J].Asian Pac J Cancer Prev,2016,17(7):3395-3403.
[30] Nouri Z,Karami F,Neyazi N,et al.Dual anti-metastatic and anti-proliferative activity assessment of two probiotics on hela and HT-29 cell lines[J].Cell J,2016,18(2):127-134.
[31] Li J,Sung CY,Lee N,et al.Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice[J].Proc Natl Acad Sci U S A,2016,113(9):E1306-15.
[32] Zhou H,He Z,Wang C,et al.Intravenous administration is an effective and safe route for cancer gene therapy using the bifidobacterium-mediated recombinant HSV-1 thymidine kinase and ganciclovir[J].Int J Mol Sci,2016,17(6).pii:E891.
[33] Brouns F,Kettlitz B,Arrigoni E.Resistant starch and "the butyrate revolution"[J].Trends Food Sci Tech,2002,13(8):251-261.
[34] Panebianco C,Adamberg K,Adamberg S,et al.Engineered resistant-starch(ERS) diet shapes colon microbiota profile in parallel with the retardation of tumor growth in vitro and in vivo pancreatic cancer models[J].Nutrients,2017,9(4).pii:E331.
[35] Kelly JR,Kennedy PJ,Cryan JF,et al.Breaking down the barriers:the gut microbiome,intestinal permeability and stress-related psychiatric disorders[J].Front Cell Neurosci,2015,9:392.
[36] Bowen JM,Stringer AM,Gibson RJ,et al.VSL#3 probiotic treatment reduces chemotherapy-induced diarrhea and weight loss[J].Cancer Biol Ther,2007,6(9):1449-1454.
[37] Osterlund P,Ruotsalainen T,Korpela R,et al.Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer:a randomised study[J].Br J Cancer 2007,97(8):1028-1034.
[38] Kato S,Hamouda N,Kano Y,et al.Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses[J].Clin Exp Pharmacol Physiol,2017,44(10):1017-1025.
[39] Mi H,Dong Y,Zhang B,et al.Bifidobacterium infantis ameliorates chemotherapy-induced intestinal mucositis via regulating T cell immunity in colorectal cancer rats[J].Cell Physiol Biochem,2017,42(6):2330-2341.
[40] Sharma A,Tilak T,Bakhshi S,et al.Lactobacillus brevis CD2 lozenges prevent oral mucositis in patients undergoing high dose chemotherapy followed by haematopoietic stem cell transplantation[J].ESMO Open,2017,1(6):e000138.
[41] Sharma A,K Rath GK,Chaudhary SP,et al.Lactobacillus brevis CD2 lozenges reduce radiation- and chemotherapy-induced mucositis in patients with head and neck cancer:a randomized double-blind placebo-controlled study[J].Eur J Cancer,2012,48(6):875-881.
[42] Mauger CA,Butler RN,Geier MS,et al.Probiotic effects on 5-fluorouracil-induced mucositis assessed by the sucrose breath test in rats[J].Dig Dis Sci,2007,52(3):612-619.
[43] Schoener CA,Carillo-Conde B,Hutson HN,et al.An inulin and doxorubicin conjugate for improving cancer therapy[J].J Drug Deliv Sci Technol,2013,23(2):111-118.
[44] Motoori M,Yano M,Miyata H,et al.Randomized study of the effect of synbiotics during neoadjuvant chemotherapy on adverse events in esophageal cancer patients[J].Clin Nutr,2017,36(1):93-99.
[45] Whitford EJ,Cummins AG,Butler RN,et al.Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent 5-Fluorouracil(5-FU)[J].Cancer Biol Ther,2009,8(6):505-511.
[46] Shen S,Lim G,You Z,et al.Gut microbiota is critical for the induction of chemotherapy-induced pain[J].Nat Neurosci,2017,20(9):1213-1216.
[47] Wallace BD,Wang H,Lane KT,et al.Alleviating cancer drug toxicity by inhibiting a bacterial enzyme [J].Science,2010,330(6005):831-835.
[48] Flieger D,Klassert C,Hainke S,et al.Phase II clinical trial for prevention of delayed diarrhea with cholestyramine/levofloxacin in the second-line treatment with irinotecan biweekly in patients with metastatic colorectal carcinoma[J].Oncology,2007,72(1/2):10-16.
[49] de Jong FA,Kehrer DF,Mathijssen RH,et al.Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening:a double-blind,randomized,placebo-controlled study[J].Oncologist,2006,11(8):944-954.
[50] Rigby RJ,Carr J,Orgel K,et al.Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis[J].Gut Microbes,2016,7(5):414-423.
[51] Viaud S,Saccheri F,Mignot G,et al.The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide[J].Science,2013,342(6161):971-976.
[52] Daillère R,Vétizou M,Waldschmitt N,et al.Enterococcus hiraeand barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects[J].Immunity,2016,45(4):931-943.
[53] Iida N,Dzutsev A,Stewart CA,et al.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J].Science,2013,342(6161):967-970.
[54] Taper HS,Roberfroid MB.Nontoxic potentiation of cancer chemotherapy by dietary oligofructose or inulin[J].Nutr Cancer,2000,38(1):1-5.
[55] Taper HS,Roberfroid MB.Possible adjuvant cancer therapy by two prebiotics--inulin or oligofructose[J].In Vivo,2005,19(1):201-204.
[56] An J,Ha EM.Combination therapy of Lactobacillus plantarum supernatant and 5-fluouracil increases chemo-sensitivity in colorectal cancer cells[J].J Microbiol Biotechnol,2016,26(8):1490-1503.
[57] Geller LT,Barzily-Rokni M,Danino T,et al.Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine[J].Science,2017,357(6356):1156-1160.
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