香菇多糖的抗肿瘤作用机制研究进展
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摘要
香菇多糖是从真菌香菇的子实体中分离出来的,主要成分为β-1,3-葡聚糖,是一种具有免疫调节作用及抑制肿瘤生长的生物调剂节,主要用于肿瘤的辅助治疗,在增强放化疗疗效、减轻放化疗毒副作用、提高机体免疫力和改善预后等方面发挥作用,在临床上取得了较好的疗效,目前在国内外被广泛应用和深入研究。因此,对香菇多糖在免疫调节,抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡、自噬,抑制肿瘤细胞血管生成及肿瘤细胞上皮间质转化,以及新型纳米材料联合应用等方面的作用进行综述,为研究香菇多糖抗肿瘤作用及机制提供新的思路。
Lentinan(LNT) is isolated from the fruiting body of fungus Lentinus edodes. The main active ingredient is β-1,3-glucan,which has pivotal role in modulating immune response and inhibiting tumor cell growth. It has been widely applied in clinic for adjuvant antitumor therapy in increasing the efficacy of radiotherapy and chemotherapy, reducing toxic and side effects of antitumor therapy, and improving the body immunity and prognosis. LNT has achieved good curative effect in clinic, and it is widely used and deeply studied at home and abroad. This review aims to discuss the progress on the role of LNT in terms of immune modulation,inhibition of tumor cell proliferation, induction of apoptosis and autophagy of tumor cells, inhibition of tumor angiogenesis and epithelial-mesenchymal transition(EMT), and the antitumor effect of compound of lentinan combined with multi-walled carbon nanotube(WMWCN) and antitumor drug, which could provide scientific reference for its future research related to the mechanism underlying the antitumor activity of lentinan.
Lentinan(LNT) is isolated from the fruiting body of fungus Lentinus edodes. The main active ingredient is β-1,3-glucan,which has pivotal role in modulating immune response and inhibiting tumor cell growth. It has been widely applied in clinic for adjuvant antitumor therapy in increasing the efficacy of radiotherapy and chemotherapy, reducing toxic and side effects of antitumor therapy, and improving the body immunity and prognosis. LNT has achieved good curative effect in clinic, and it is widely used and deeply studied at home and abroad. This review aims to discuss the progress on the role of LNT in terms of immune modulation,inhibition of tumor cell proliferation, induction of apoptosis and autophagy of tumor cells, inhibition of tumor angiogenesis and epithelial-mesenchymal transition(EMT), and the antitumor effect of compound of lentinan combined with multi-walled carbon nanotube(WMWCN) and antitumor drug, which could provide scientific reference for its future research related to the mechanism underlying the antitumor activity of lentinan.
引文
[1]Chihara G,Maeda Y,Hamuro J,et al.Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes(Berk.)sing[J].Nature,1969,222(5194):687-688.
[2]Ren L,Perera C,Hemar Y.Antitumor activity of mushroom polysaccharides:A review[J].Food Funct,2012,3(11):1118-1130.
[3]Zhang Y,Zhang M,Jiang Y,et al.Lentinan as an immunotherapeutic for treating lung cancer:A review of12 years clinical studies in China[J].J Cancer Res Clin Oncol,2018,144(11):2177-2186.
[4]Bisen P S,Baghel R K,Sanodiya B S,et al.Lentinus edodes:A macrofungus with pharmacological activities[J].Curr Med Chem,2010,17(22):2419-2430.
[5]Chihara G,Hamuro J,Maeda Y Y,et al.Antitumor and metastasis-inhibitory activities of lentinan as an immunomodulator:An overview[J].Cancer Detect Prev Suppl,1987,1:423-443.
[6]程伟,邢东炜,张闽光.中药多糖调节肿瘤免疫应答研究进展[J].现代免疫学,2017,37(3):242-246.
[7]张景欣,马明.香菇多糖注射液对恶性肿瘤患者T淋巴细胞亚群及NK细胞的影响[J].中医药学报,2015,43(4):116-118.
[8]华红霞,任国琴,孙优苗,等.香菇多糖对老年乳腺癌化疗病人T细胞亚群及血清IL-2、IL-6的影响[J].实用老年医学,2017,31(2):157-160.
[9]Wang S X,Liu Q Y,Li Y.Lentinan ameliorates burn sepsis by attenuating CD4(+)CD25(+)Tregs[J].Burns,2016,42(7):1513-1521.
[10]Wang X E,Wang Y H,Zhou Q,et al.Immunomodulatory effect of lentinan on aberrant T subsets and cytokines profile in non-small cell lung cancer patients[J].Pathol Oncol Res,2018,doi:10.1007/s12253-018-0545-y.
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[12]梁金强,王园园,胡明华,等.复合多糖对CTX致免疫低下小鼠的免疫增强作用[J].中药材,2017,40(4):953-956.
[13]Luo X,Huang S,Luo S,et al.Identification of genes underlying the enhancement of immunity by a formula of lentinan,pachymaran and tremelia polysaccharides in immunosuppressive mice[J].Sci Rep,2018,8(1):10082.
[14]Arinaga S,Karimine N,Takamuku K,et al.Enhanced production of interleukin 1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma[J].Int JImmunopharmacol,1992,14(1):43-47.
[15]吴小清,陈鸿策,芮雯,等.香菇多糖对人肺腺癌细胞A549免疫原性死亡相关分子表达的影响[J].转化医学电子杂志,2018,5(4):16-20.
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[17]丁航,侯敢,周克元,等.香菇多糖对巨噬细胞一氧化氦和一氧化氦合酶活性的影响[J].广东药学,2003,13(4):32-33.
[18]胡明华,邓向亮,徐路.香菇茯苓银耳复合多糖对小鼠巨噬细胞功能的作用研究[J].中国免疫学杂志,2018,34(1):44-49.
[19]Liu Y,Zhao J,Zhao Y,et al.Therapeutic effects of lentinan on inflammatory bowel disease and colitis-associated cancer[J].J Cell Mol Med,2019,23(2):750-760.
[20]Suga Y,Takehana K.Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1administration[J].Int Immunopharmacol,2017,50:55-60.
[21]桂明杰,亢学平,王鑫,等.香菇多糖对Hep G2及H22肿瘤细胞的抑制研究[J].食用菌,2015(5):63-65.
[22]李雪梅,胡宇驰.注射用香菇多糖的抗肿瘤效应量效关系考察试验研究[J].药学研究,2014,33(10):564-566.
[23]Wang J,Li W,Huang X,et al.A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice[J].Oncotarget,2017,8(1):610-623.
[24]Floor S L,Dumont J E,Maenhaut C,et al.Hallmarks of cancer:Of all cancer cells,all the time?[J].Trends Mol Med,2012,18(9):509-515.
[25]Lazebnik Y.What are the hallmarks of cancer?[J].Nat Rev Cancer,2010,10(4):232-233.
[26]颜亚楠,王晶晶,袁毅,等.香菇多糖对口腔鳞癌细胞增殖的影响[J].口腔生物医学,2018,9(2):79-81.
[27]Zi Y,Zhang B,Jiang B,et al.Antioxidant action and protective and reparative effects of lentinan on oxidative damage in HaCaT cells[J].J Cosmet Dermatol,2018,17(6):1108-1114.
[28]Bao L,Wang Y,Ma R,et al.Apoptosis-inducing effects of lentinan on the proliferation of human bladder cancer T24 cells[J].Pak J Pharm Sci,2015,28(5):1595-1600.
[29]Zhao L,Xiao Y,Xiao N.Effect of lentinan combined with docetaxel and cisplatin on the proliferation and apoptosis of BGC823 cells[J].Tumour Biol,2013,34(3):1531-1536.
[30]Sun M,Zhao W,Xie Q,et al.Lentinan reduces tumor progression by enhancing gemcitabine chemotherapy in urothelial bladder cancer[J].Surg Oncol,2015,24(1):28-34.
[31]Liu W,Gu J,Qi J,et al.Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome[J].J Cell Mol Med,2015,19(8):1949-1955.
[32]Attia S M,Harisa G I,Abd-Allah A R,et al.The influence of lentinan on the capacity of repair of DNAdamage and apoptosis induced by paclitaxel in mouse bone marrow cells[J].J Biochem Mol Toxicol,2013,27(7):370-377.
[33]Zhang Y,Li Q,Wang J,et al.Polysaccharide from Lentinus edodes combined with oxaliplatin possesses the synergy and attenuation effect in hepatocellular carcinoma[J].Cancer Lett,2016,377(2):117-125.
[34]Ya G.A Lentinus edodes polysaccharide induces mitochondrial-mediated apoptosis in human cervical carcinoma HeLa cells[J].Int J Biol Macromol,2017,103:676-682.
[35]李学波,孙瑶,李乃坤,等.香菇多糖对老年中晚期消化道恶性肿瘤患者C3、CD3、CD4及CD4/CD8比值的影响[J].中国老年学杂志,2017,37(12):2964-2965.
[36]陈军.香菇多糖注射液联合化疗治疗中晚期胃癌的临床疗效观察[J].中国保健营养,2016,26(13):45.
[37]Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.
[38]Deng S,Zhang G,Kuai J,et al.Lentinan inhibits tumor angiogenesis via interferon gamma and in a T cell independent manner[J].J Exp Clin Cancer Res,2018,37(1):260-272.
[39]朱青静.香菇多糖体外抗血管生成作用实验研究[J].中医学报,2017,32(12):2426-2429.
[40]Li W,Wang J,Hu H,et al.Functional polysaccharide lentinan suppresses human breast cancer growth via inducing autophagy and caspase-7-mediated apoptosis[J].J Funct Foods,2018,45:75-85.
[41]Dongre A,Weinberg R A.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer[J].Nat Rev Mol Cell Biol,2019,20(2):69-84.
[42]Liu Y R,Sun B,Zhu G H,et al.Selenium-lentinan inhibits tumor progression by regulating epithelialmesenchymal transition[J].Toxicol Appl Pharmacol,2018,360:1-8.
[43]Xing J,Liu Z,Huang Y,et al.Lentinan-modified carbon nanotubes as an antigen delivery system modulate immune response in vitro and in vivo[J].ACS Appl Mater Interfaces,2016,8(30):19276-19283.
[44]Vandyke D,Kyriacopulos P,Yassini B,et al.Nanoparticle based combination treatments for targeting multiple hallmarks of cancer[J].Int J Nano Stud Technol,2016,doi:10.19070/2167-8685-SI04001.
[45]Zhang P,Yi W,Hou J,et al.A carbon nanotubegemcitabine-lentinan three-component composite for chemo-photothermal synergistic therapy of cancer[J].Int J Nanomed,2018,13:3069-3080.
[46]Yi W,Zhang P,Hou J,et al.Enhanced response of tamoxifen toward the cancer cells using a combination of chemotherapy and photothermal ablation induced by lentinan-functionalized multi-walled carbon nanotubes[J].Int J Biol Macromol,2018,120(Pt B):1525-1532.
[47]龙进,涂文升.香菇多糖注射液在肿瘤治疗中的配伍应用[J].中国现代药物应用,2016,10(8):270-271.
[2]Ren L,Perera C,Hemar Y.Antitumor activity of mushroom polysaccharides:A review[J].Food Funct,2012,3(11):1118-1130.
[3]Zhang Y,Zhang M,Jiang Y,et al.Lentinan as an immunotherapeutic for treating lung cancer:A review of12 years clinical studies in China[J].J Cancer Res Clin Oncol,2018,144(11):2177-2186.
[4]Bisen P S,Baghel R K,Sanodiya B S,et al.Lentinus edodes:A macrofungus with pharmacological activities[J].Curr Med Chem,2010,17(22):2419-2430.
[5]Chihara G,Hamuro J,Maeda Y Y,et al.Antitumor and metastasis-inhibitory activities of lentinan as an immunomodulator:An overview[J].Cancer Detect Prev Suppl,1987,1:423-443.
[6]程伟,邢东炜,张闽光.中药多糖调节肿瘤免疫应答研究进展[J].现代免疫学,2017,37(3):242-246.
[7]张景欣,马明.香菇多糖注射液对恶性肿瘤患者T淋巴细胞亚群及NK细胞的影响[J].中医药学报,2015,43(4):116-118.
[8]华红霞,任国琴,孙优苗,等.香菇多糖对老年乳腺癌化疗病人T细胞亚群及血清IL-2、IL-6的影响[J].实用老年医学,2017,31(2):157-160.
[9]Wang S X,Liu Q Y,Li Y.Lentinan ameliorates burn sepsis by attenuating CD4(+)CD25(+)Tregs[J].Burns,2016,42(7):1513-1521.
[10]Wang X E,Wang Y H,Zhou Q,et al.Immunomodulatory effect of lentinan on aberrant T subsets and cytokines profile in non-small cell lung cancer patients[J].Pathol Oncol Res,2018,doi:10.1007/s12253-018-0545-y.
[11]南君,许春进.香菇多糖配合化疗对肝癌患者肝功能、T细胞亚群及IL-12、sIL-2R的影响[J].中西医结合肝病杂志,2018,28(3):153-155.
[12]梁金强,王园园,胡明华,等.复合多糖对CTX致免疫低下小鼠的免疫增强作用[J].中药材,2017,40(4):953-956.
[13]Luo X,Huang S,Luo S,et al.Identification of genes underlying the enhancement of immunity by a formula of lentinan,pachymaran and tremelia polysaccharides in immunosuppressive mice[J].Sci Rep,2018,8(1):10082.
[14]Arinaga S,Karimine N,Takamuku K,et al.Enhanced production of interleukin 1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma[J].Int JImmunopharmacol,1992,14(1):43-47.
[15]吴小清,陈鸿策,芮雯,等.香菇多糖对人肺腺癌细胞A549免疫原性死亡相关分子表达的影响[J].转化医学电子杂志,2018,5(4):16-20.
[16]Fukuchi M,Mochiki E,Ishiguro T,et al.Evaluation of immunity in elderly patients with unresectable gastric cancer receiving S-1/lentinan combination chemotherapy[J].Gan To Kagaku Ryoho,2014,41(10):1264-1266.
[17]丁航,侯敢,周克元,等.香菇多糖对巨噬细胞一氧化氦和一氧化氦合酶活性的影响[J].广东药学,2003,13(4):32-33.
[18]胡明华,邓向亮,徐路.香菇茯苓银耳复合多糖对小鼠巨噬细胞功能的作用研究[J].中国免疫学杂志,2018,34(1):44-49.
[19]Liu Y,Zhao J,Zhao Y,et al.Therapeutic effects of lentinan on inflammatory bowel disease and colitis-associated cancer[J].J Cell Mol Med,2019,23(2):750-760.
[20]Suga Y,Takehana K.Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1administration[J].Int Immunopharmacol,2017,50:55-60.
[21]桂明杰,亢学平,王鑫,等.香菇多糖对Hep G2及H22肿瘤细胞的抑制研究[J].食用菌,2015(5):63-65.
[22]李雪梅,胡宇驰.注射用香菇多糖的抗肿瘤效应量效关系考察试验研究[J].药学研究,2014,33(10):564-566.
[23]Wang J,Li W,Huang X,et al.A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice[J].Oncotarget,2017,8(1):610-623.
[24]Floor S L,Dumont J E,Maenhaut C,et al.Hallmarks of cancer:Of all cancer cells,all the time?[J].Trends Mol Med,2012,18(9):509-515.
[25]Lazebnik Y.What are the hallmarks of cancer?[J].Nat Rev Cancer,2010,10(4):232-233.
[26]颜亚楠,王晶晶,袁毅,等.香菇多糖对口腔鳞癌细胞增殖的影响[J].口腔生物医学,2018,9(2):79-81.
[27]Zi Y,Zhang B,Jiang B,et al.Antioxidant action and protective and reparative effects of lentinan on oxidative damage in HaCaT cells[J].J Cosmet Dermatol,2018,17(6):1108-1114.
[28]Bao L,Wang Y,Ma R,et al.Apoptosis-inducing effects of lentinan on the proliferation of human bladder cancer T24 cells[J].Pak J Pharm Sci,2015,28(5):1595-1600.
[29]Zhao L,Xiao Y,Xiao N.Effect of lentinan combined with docetaxel and cisplatin on the proliferation and apoptosis of BGC823 cells[J].Tumour Biol,2013,34(3):1531-1536.
[30]Sun M,Zhao W,Xie Q,et al.Lentinan reduces tumor progression by enhancing gemcitabine chemotherapy in urothelial bladder cancer[J].Surg Oncol,2015,24(1):28-34.
[31]Liu W,Gu J,Qi J,et al.Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome[J].J Cell Mol Med,2015,19(8):1949-1955.
[32]Attia S M,Harisa G I,Abd-Allah A R,et al.The influence of lentinan on the capacity of repair of DNAdamage and apoptosis induced by paclitaxel in mouse bone marrow cells[J].J Biochem Mol Toxicol,2013,27(7):370-377.
[33]Zhang Y,Li Q,Wang J,et al.Polysaccharide from Lentinus edodes combined with oxaliplatin possesses the synergy and attenuation effect in hepatocellular carcinoma[J].Cancer Lett,2016,377(2):117-125.
[34]Ya G.A Lentinus edodes polysaccharide induces mitochondrial-mediated apoptosis in human cervical carcinoma HeLa cells[J].Int J Biol Macromol,2017,103:676-682.
[35]李学波,孙瑶,李乃坤,等.香菇多糖对老年中晚期消化道恶性肿瘤患者C3、CD3、CD4及CD4/CD8比值的影响[J].中国老年学杂志,2017,37(12):2964-2965.
[36]陈军.香菇多糖注射液联合化疗治疗中晚期胃癌的临床疗效观察[J].中国保健营养,2016,26(13):45.
[37]Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.
[38]Deng S,Zhang G,Kuai J,et al.Lentinan inhibits tumor angiogenesis via interferon gamma and in a T cell independent manner[J].J Exp Clin Cancer Res,2018,37(1):260-272.
[39]朱青静.香菇多糖体外抗血管生成作用实验研究[J].中医学报,2017,32(12):2426-2429.
[40]Li W,Wang J,Hu H,et al.Functional polysaccharide lentinan suppresses human breast cancer growth via inducing autophagy and caspase-7-mediated apoptosis[J].J Funct Foods,2018,45:75-85.
[41]Dongre A,Weinberg R A.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer[J].Nat Rev Mol Cell Biol,2019,20(2):69-84.
[42]Liu Y R,Sun B,Zhu G H,et al.Selenium-lentinan inhibits tumor progression by regulating epithelialmesenchymal transition[J].Toxicol Appl Pharmacol,2018,360:1-8.
[43]Xing J,Liu Z,Huang Y,et al.Lentinan-modified carbon nanotubes as an antigen delivery system modulate immune response in vitro and in vivo[J].ACS Appl Mater Interfaces,2016,8(30):19276-19283.
[44]Vandyke D,Kyriacopulos P,Yassini B,et al.Nanoparticle based combination treatments for targeting multiple hallmarks of cancer[J].Int J Nano Stud Technol,2016,doi:10.19070/2167-8685-SI04001.
[45]Zhang P,Yi W,Hou J,et al.A carbon nanotubegemcitabine-lentinan three-component composite for chemo-photothermal synergistic therapy of cancer[J].Int J Nanomed,2018,13:3069-3080.
[46]Yi W,Zhang P,Hou J,et al.Enhanced response of tamoxifen toward the cancer cells using a combination of chemotherapy and photothermal ablation induced by lentinan-functionalized multi-walled carbon nanotubes[J].Int J Biol Macromol,2018,120(Pt B):1525-1532.
[47]龙进,涂文升.香菇多糖注射液在肿瘤治疗中的配伍应用[J].中国现代药物应用,2016,10(8):270-271.
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