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研究生:蘇子婷
研究生(外文):SU, TZU-TING
論文名稱:探討植物多醣對腫瘤細胞免疫原性死亡和免疫活化之影響:以中藥黃耆為例
論文名稱(外文):Investigation of the Phytopolysaccharides on Immunogenic Cell Death of Tumor Cells and Immune Activation: Lessons Learned from Astragalus Membranaceus
指導教授:黃文經黃文經引用關係魏紋祈
指導教授(外文):HUANG, WEN-CHINGWEI, WEN-CHI
口試委員:黃啟彰
口試委員(外文):HUANG, CHI-CHANG
口試日期:2020-06-29
學位類別:碩士
校院名稱:國立臺北護理健康大學
系所名稱:運動保健研究所
學門:民生學門
學類:運動休閒及休閒管理學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:48
中文關鍵詞:乳癌黃耆樹突狀細胞提升免疫運動
外文關鍵詞:Breast cancerAstragalus membranaceusImmunotherapyDendritic cell
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由於全球癌症發生率不斷上升,癌症已經成為危害全人類健康最為重要的疾病。在癌症治療上,除了以化療藥物毒殺癌細胞的傳統療法外,免疫療法藉由活化免疫反應來達到抗癌療效,已被視為癌症治療的新契機。中藥黃耆被認為具有提升免疫力及抗癌之功效。為了開發可以增強癌症免疫療法之輔助品,本研究探討黃耆多醣對腫瘤細胞免疫原性死亡和免疫活化之影響,透過酵素免疫吸附分析法來檢測小鼠骨髓源性樹突狀細胞在黃耆的誘導下,樹突狀細胞的細胞激素是否有所影響。本研究初步結果顯示,黃耆萃取物能有效提高樹突狀細胞 TNF-α、IL6、IL-12、IL-23 表現量,但對於黃耆誘導腫瘤細胞產生免疫原性死亡以及免疫檢查點分子 PDL1 的表現並無顯著提升,未來我們將進一步以腫瘤動物驗模式與運動合併介入,評估黃耆萃取物作為增強免疫與抑制腫瘤轉移之效果並開發出具有可以改善癌症病患及提供未來臨床應用之科學理論基礎,未來更進一步結合運動與中草藥介入對於癌症治療更應具應用價值。
As the global incidence of cancer continues to rise, cancer has become the most common harmful disease worldwide. Different from chemotherapy by killing tumor cells, cancer immunotherapy is treatment that boosts the body's immune system to fight cancer and is recognized as a promising treatment for cancer. Astragalus membranaceus a well-known traditional Chinese medicinal herb has been reported to have immunomodulatory and anti-cancer activities. In this study, we investigated the effect of Astragalus polysaccharides on immunogenic cell death of tumor cells and immune activation for enhancement of cancer immunotherapy. Our preliminary data showed that Astragalus polysaccharides effectively stimulated the expression of TNF-α, IL-6, IL-12 and IL-23 in dendritic cells. However, there was no significant improvement in the performance of immunogenic cell death of tumor cells and immune checkpoint molecule PDL1 by Astragalus polysaccharides. We will ifurther nvestigate the anti-cancer activity of Astragalus polysaccharides in an animal model. We believe that the results in the present study could provide the scientific evidence for clinical application of traditional Chinese medicines in the future.
中文摘要………………………………………………………………………i
英文摘要………………………………………………………………………ii
目次………………………………………………………………………………iii
圖次………………………………………………………………………………v
第一章 緒論
第一節 研究背景與動機…………………………………………………………1
第二節 研究目的與假設…………………………………………………………5
第二章 文獻探討
第一節 免疫檢查點 (Immune checkpoint)……………………………………6
第二節 免疫原性細胞死亡 (immunogenic cell death, ICD)……………………8
第三節 樹突狀細胞……………………………………………………………10
第四節 中草藥黃耆……………………………………………………………12
第三章 研究方法與材料
第一節 實驗材料………………………………………………………………14
第二節 實驗內容………………………………………………………………16
第四節 實驗設計與方法…………………………………………………20
第五節 統計分析………………………………………………………………20
第四章 結果
第一節 黃耆對不同細胞株之細胞存活率…………………………………21
第二節 觀察樹突狀細胞在黃耆誘導下之細胞型態………………………23
第三節 樹突狀細胞的分化成熟度與細胞表面抗原的表現…………………24
第四節 黃耆對樹突狀細胞之細胞激素分析…………………………………26
第五節 以黃耆誘導樹突狀細胞之內噬效果…………………………………28
第六節 黃耆誘導 4T1 細胞的免疫原性死亡與免疫查哨分子表現…………29
第五章 討論…………………………………………………………………31
第六章 結論…………………………………………………………………34
參考文獻…………………………………………………………………………35
附件一………………………………………………………………………………40
Alvarez, D., Vollmann, E. H., & von Andrian, U. H. (2008). Mechanisms and consequences of dendritic cell migration. Immunity, 29(3), 325-342. doi:10.1016/j.immuni.2008.08.006

Bartsch, R., Wenzel, C., & Steger, G. G. (2007). Trastuzumab in the management of early and advanced stage breast cancer. Biologics, 1(1), 19-31.

Chang, W. T., Chen, H. M., Yin, S. Y., Chen, Y. H., Wen, C. C., Wei, W. C., . . . Yang, N. S. (2013). Specific Dioscorea Phytoextracts Enhance Potency of TCLLoaded DC-Based Cancer Vaccines. Evid Based Complement Alternat Med, 2013, 932040. doi:10.1155/2013/932040

Chang, W. T., Lai, T. H., Chyan, Y. J., Yin, S. Y., Chen, Y. H., Wei, W. C., & Yang, N. S. (2015). Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mouse mammary tumor metastasis. PLoS One, 10(3), e0122374. doi:10.1371/journal.pone.0122374

Chao, M. P., Jaiswal, S., Weissman-Tsukamoto, R., Alizadeh, A. A., Gentles, A. J., Volkmer, J., . . . Weissman, I. L. (2010). Calreticulin is the dominant prophagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med, 2(63), 63ra94. doi:10.1126/scitranslmed.3001375

Chen, H. M., Wang, P. H., Chen, S. S., Wen, C. C., Chen, Y. H., Yang, W. C., & Yang, N. S. (2012). Shikonin induces immunogenic cell death in tumor cells and
enhances dendritic cell-based cancer vaccine. Cancer Immunol Immunother, 61(11), 1989-2002. doi:10.1007/s00262-012-1258-9

Cheng, Y., Tang, K., Wu, S., Liu, L., Qiang, C., Lin, X., & Liu, B. (2011). Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins. PLoS One, 6(11), e27437. doi:10.1371/journal.pone.0027437 Drake, C. G. (2010). Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol, 10(8), 580-593. doi:10.1038/nri2817

Du, X., Zhao, B., Li, J., Cao, X., Diao, M., Feng, H., . . . Zeng, X. (2012). Astragalus polysaccharides enhance immune responses of HBV DNA vaccination via promoting the dendritic cell maturation and suppressing Treg frequency in mice.
Int Immunopharmacol, 14(4), 463-470. doi:10.1016/j.intimp.2012.09.006

Elsabahy, M., & Wooley, K. L. (2013). Cytokines as biomarkers of nanoparticle immunotoxicity. Chem Soc Rev, 42(12), 5552-5576. doi:10.1039/c3cs60064e

Gibney, G. T., Weiner, L. M., & Atkins, M. B. (2016). Predictive biomarkers for
checkpoint inhibitor-based immunotherapy. Lancet Oncol, 17(12), e542-e551. doi:10.1016/s1470-2045(16)30406-5

Gonzalez, F. E., Gleisner, A., Falcon-Beas, F., Osorio, F., Lopez, M. N., & Salazar-Onfray, F. (2014). Tumor cell lysates as immunogenic sources for cancer
vaccine design. Hum Vaccin Immunother, 10(11), 3261-3269. doi:10.4161/21645515.2014.982996

Gupta, G. P., & Massague, J. (2006). Cancer metastasis: building a framework. Cell, 127(4), 679-695. doi:10.1016/j.cell.2006.11.001

Hamuti, A., Li, J., Zhou, F., Aipire, A., Ma, J., Yang, J., & Li, J. (2017). Capparis spinosa Fruit Ethanol Extracts Exert Different Effects on the Maturation of Dendritic Cells. Molecules, 22(1). doi:10.3390/molecules22010097

Harbeck, N., & Gnant, M. (2017). Breast cancer. Lancet, 389(10074), 1134-1150.
doi:10.1016/s0140-6736(16)31891-8

Hatfield, P., Merrick, A. E., West, E., O'Donnell, D., Selby, P., Vile, R., & Melcher, A. A. (2008). Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J Immunother, 31(7), 620-632. doi:10.1097/CJI.0b013e31818213df

Huang, W. M., Liang, Y. Q., Tang, L. J., Ding, Y., & Wang, X. H. (2013). Antioxidant and anti-inflammatory effects of Astragalus polysaccharide on EA.hy926 cells. Exp Ther Med, 6(1), 199-203. doi:10.3892/etm.2013.1074

Hubo, M., Trinschek, B., Kryczanowsky, F., Tuettenberg, A., Steinbrink, K., & Jonuleit, H. (2013). Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells. Front Immunol, 4, 82. doi:10.3389/fimmu.2013.00082

Husemann, Y., Geigl, J. B., Schubert, F., Musiani, P., Meyer, M., Burghart, E., . . . Klein, C. A. (2008). Systemic spread is an early step in breast cancer. Cancer Cell, 13(1), 58-68. doi:10.1016/j.ccr.2007.12.003

Jesinger, R. A. (2014). Breast anatomy for the interventionalist. Tech Vasc Interv Radiol, 17(1), 3-9. doi:10.1053/j.tvir.2013.12.002

Jiang, Y., Qi, X., Gao, K., Liu, W., Li, N., Cheng, N., . . . Xiao, W. (2016). Relationship between molecular weight, monosaccharide composition and immunobiologic activity of Astragalus polysaccharides. Glycoconj J, 33(5), 755-761. doi:10.1007/s10719-016-9669-z

Juan, Y. C., Kuo, Y. H., Chang, C. C., Zhang, L. J., Lin, Y. Y., Hsu, C. Y., & Liu, H. K. (2011). Administration of a decoction of sucrose- and polysaccharide-rich radix astragali (huang qi) ameliorated insulin resistance and Fatty liver but affected Beta-cell function in type 2 diabetic rats. Evid Based Complement Alternat Med, 2011, 349807. doi:10.1155/2011/349807

Kallon, S., Li, X., Ji, J., Chen, C., Xi, Q., Chang, S., . . . Zhang, Y. (2013). Astragalus polysaccharide enhances immunity and inhibits H9N2 avian influenza virus in vitro and in vivo. J Anim Sci Biotechnol, 4(1), 22. doi:10.1186/2049-1891-4-22

Kang, H., Ahn, K. S., Cho, C., & Bae, H. S. (2004). Immunomodulatory effect of Astragali Radix extract on murine TH1/TH2 cell lineage development. Biol
Pharm Bull, 27(12), 1946-1950. doi:10.1248/bpb.27.1946

Kroemer, G., Galluzzi, L., Kepp, O., & Zitvogel, L. (2013). Immunogenic cell death in cancer therapy. Annu Rev Immunol, 31, 51-72. doi:10.1146/annurev-immunol032712-100008

Kyi, C., & Postow, M. A. (2014). Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett, 588(2), 368-376. doi:10.1016/j.febslet.2013.10.015

Latz, E., Xiao, T. S., & Stutz, A. (2013). Activation and regulation of the inflammasomes. Nat Rev Immunol, 13(6), 397-411. doi:10.1038/nri3452

Li, X., He, X., Liu, B., Xu, L., Lu, C., Zhao, H., . . . Lu, A. (2012). Maturation of murine bone marrow-derived dendritic cells induced by Radix Glycyrrhizae polysaccharide. Molecules, 17(6), 6557-6568. doi:10.3390/molecules17066557

Li, W., Song, K., Wang, S., Zhang, C., Zhuang, M., Wang, Y., & Liu, T. (2019). Antitumor potential of astragalus polysaccharides on breast cancer cell line mediated by macrophage activation. Mater Sci Eng C Mater Biol Appl, 98, 685-695. doi:10.1016/j.msec.2019.01.025

Lin, J., Kang, H., Liang, J., Fu, J., Yu, Q., & Yang, Q. (2015). CpG oligonucleotides and Astragalus polysaccharides are effective adjuvants in cultures of avian bone-marrow-derived dendritic cells. Br Poult Sci, 56(1), 30-38. doi:10.1080/00071668.2014.981146

Linnek, J., Mitaine-Offer, A. C., Miyamoto, T., Duchamp, O., Mirjolet, J. F., &
Lacaille-Dubois, M. A. (2009). Cycloartane-type glycosides from two species of Astragalus (Fabaceae). Nat Prod Commun, 4(4), 477-478.

Liu, Q. Y., Yao, Y. M., Zhang, S. W., & Sheng, Z. Y. (2011). Astragalus polysaccharides regulate T cell-mediated immunity via CD11c(high)CD45RB(low) DCs in vitro. J Ethnopharmacol, 136(3), 457-464. doi:10.1016/j.jep.2010.06.041

Lotze, M. T., & DeMarco, R. A. (2003). Dealing with death: HMGB1 as a novel target for cancer therapy. Curr Opin Investig Drugs, 4(12), 1405-1409.

Meng, Y., Gao, X., Chen, W., Plotnikoff, N. P., Griffin, N., Zhang, G., & Shan, F. (2017). Methionine enkephalin (MENK) mounts antitumor effect via regulating
dendritic cells (DCs). Int Immunopharmacol, 44, 61-71. doi:10.1016/j.intimp.2017.01.004

Mohsin, S. K., Weiss, H. L., Gutierrez, M. C., Chamness, G. C., Schiff, R., Digiovanna, M. P., . . . Chang, J. C. (2005). Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol, 23(11), 2460-2468.
doi:10.1200/jco.2005.00.661

Morin, P. J. (1999). beta-catenin signaling and cancer. Bioessays, 21(12), 1021-1030. doi:10.1002/(sici)1521-1878(199912)22:1<1021::Aid-bies6>3.0.Co;2-p

Nabeshima, S., Murata, M., Hamada, M., Chong, Y., Yamaji, K., & Hayashi, J. (2004). Maturation of monocyte-derived dendritic cells by Hochu-ekki-to, a traditional Japanese herbal medicine. Int Immunopharmacol, 4(1), 37-45.
doi:10.1016/j.intimp.2003.10.002

Nagarsheth, N., Wicha, M. S., & Zou, W. (2017). Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol, 17(9), 559-572. doi:10.1038/nri.2017.49

Palucka, K., & Banchereau, J. (2013). Dendritic-cell-based therapeutic cancer vaccines. Immunity, 39(1), 38-48. doi:10.1016/j.immuni.2013.07.004

Park, J. W., Melisko, M. E., Esserman, L. J., Jones, L. A., Wollan, J. B., & Sims, R. (2007). Treatment with autologous antigen-presenting cells activated with the HER-2 based antigen Lapuleucel-T: results of a phase I study in immunologic and clinical activity in HER-2 overexpressing breast cancer. J Clin Oncol, 25(24), 3680-3687. doi:10.1200/jco.2006.10.5718

Peart, O. (2015). Breast intervention and breast cancer treatment options. Radiol Technol, 86(5), 535M-558M; quiz 559-562.

Santander, S. P., Hernández, J. F., Barreto, C. C., Masayuki, A., Moins-Teisserenc, H., & Fiorentino, S. (2012). Immunomodulatory effects of aqueous and organic fractions from Petiveria alliacea on human dendritic cells. Am J Chin Med, 40(4), 833-844. doi:10.1142/s0192415x12500620

Shao, P., Zhao, L. H., Zhi, C., & Pan, J. P. (2006). Regulation on maturation and function of dendritic cells by Astragalus mongholicus polysaccharides. Int
Immunopharmacol, 6(7), 1161-1166. doi:10.1016/j.intimp.2006.02.009

Song, Y., Yang, J., Bai, W. L., & Ji, W. Y. (2011). Antitumor and immunoregulatory effects of astragalus on nasopharyngeal carcinoma in vivo and in vitro. Phytother Res, 25(6), 909-915. doi:10.1002/ptr.3354

Steinman, R. M., & Cohn, Z. A. (1973). Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med, 137(5), 1142-1162. doi:10.1084/jem.137.5.1142

Sun, T. Y., Yan, W., Yang, C. M., Zhang, L. F., Tang, H. L., Chen, Y., . . . Wei, X. (2015). Clinical research on dendritic cell vaccines to prevent postoperative recurrence and metastasis of liver cancer. Genet Mol Res, 14(4), 16222-16232. doi:10.4238/2015.December.8.12

Wei, W., Xiao, H. T., Bao, W. R., Ma, D. L., Leung, C. H., Han, X. Q., . . . Han, Q. B. (2016). TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells. J Ethnopharmacol, 179, 243-252. doi:10.1016/j.jep.2015.12.060

Whitesell, L., & Lindquist, S. L. (2005). HSP90 and the chaperoning of cancer. Nat Rev Cancer, 5(10), 761-772. doi:10.1038/nrc1716

Wykes, M. N., & Lewin, S. R. (2018). Immune checkpoint blockade in infectious
diseases. Nat Rev Immunol, 18(2), 91-104. doi:10.1038/nri.2017.112

Yin, S. Y., Wei, W. C., Jian, F. Y., & Yang, N. S. (2013). Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med, 2013, 302426. doi:10.1155/2013/302426

Zheng, Y., Ren, W., Zhang, L., Zhang, Y., Liu, D., & Liu, Y. (2020). A Review of the Pharmacological Action of Astragalus Polysaccharide. Front Pharmacol, 11, 349. doi:10.3389/fphar.2020.00349

Zhou, R., Chen, H., Chen, J., Chen, X., Wen, Y., & Xu, L. (2018). Extract from
Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway. BMC Complement Altern Med, 18(1), 83.
doi:10.1186/s12906-018-2148-2

Zurrida, S., & Veronesi, U. (2015). Milestones in breast cancer treatment. Breast J, 21(1), 3-12. doi:10.1111/tbj.12361
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