博碩士論文 109826601 詳細資訊




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姓名 阮氏菊香(Nguyen Thi Cuc Huong)  查詢紙本館藏   畢業系所 系統生物與生物資訊研究所
論文名稱 探索 BP010W 的治療潛力:基於雌激素信號通路, 以澳洲茄胺作為抑製劑研究肺癌細胞遷移的綜合分析
(Exploring the Therapeutic Potential of BP010W: A Comprehensive Analysis of Solasodine as an Inhibitor of Lung Cancer Cell Migration via the Estrogen Signalling Pathway)
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摘要(中) 癌症發病率在全球範圍內迅速增長,包括台灣在內,肺癌成為一個突出的問題。由於癌細胞的侵襲性,患者常常在被檢測和治療之前就達到了3期。近年來,東方醫學作為一種經濟高效、綜合全面的治療方法受到了廣泛關注。該研究使用了BP010W在100 μg/ml濃度下的數據,通過36小時的實驗組展示了其出色的抑制肺癌細胞遷移的能力。使用DAVID程序對包含1375個基因的進一步分析表明可能參與了雌激素信號通路,為未來的研究提供了前景,並驗證了研究結果。發現了三條獨立的遷移途徑,並且結果顯示與雌激素信號系統相關的基因明顯下調,特別是MMP13、ZEB1、SNAI1、VIM、CDH2和ICAM1。此外,使用連接圖譜(cMap)對33個上調基因和150個下調基因進行比較,展示了Erteberel及其與雌激素信號通路的關係。該研究進一步證實了BP010W通過調節雌激素信號系統來減少肺癌細胞遷移的能力。 BP010W中被確認的組分之一,Solasodine,顯示出對肺癌細胞具有強效的抑製作用。包括細胞阻塞試驗和存活性評估在內的實驗顯示了雌激素的促遷移效應以及Solasodine在限制遷移中的關鍵作用。
摘要(英) Cancer incidence is quickly growing globally, including in Taiwan, with lung cancer being a prominent concern. Because of the aggressive nature of cancer cell migration, patients frequently reach stage 3 before being detected and treated. Oriental medicine has received a lot of attention in recent years as a cost-effective and comprehensive approach to treatment. The study uses data from BP010W at a concentration of 100 μg/ml in a 36-hour group to demonstrate its extraordinary ability to block lung cancer cell migration. Further analysis encompassing 1375 genes using the DAVID program suggests a likely participation of the estrogen pathway, giving prospects for future research and validating the study′s findings. Three separate migratory routes are discovered, and the results show a considerable downregulation of genes linked with the estrogen signalling system, notably MMP13, ZEB1, SNAI1, VIM, CDH2 and ICAM1. Furthermore, using the Connectivity Map (cMap) to compare 33 up-regulated genes and 150 down-regulated genes demonstrates erteberel and its relationship with the estrogen signalling pathway. This study adds to the evidence that BP010W has the ability to reduce lung cancer cell migration via modulating the estrogen signalling system. Solasodine, one of the recognized components of BP010W, appears as a significant element with potent inhibitory effects on lung cancer cells. Experiments, including cell-blocking tests and viability evaluations, show estrogen′s pro-migratory effect and the critical role of Solasodine in limiting migration.
關鍵字(中) ★ 肺癌
★ 中醫藥
★ 雌激素通路
★ 連接圖譜
★ 遷移
關鍵字(英) ★ Lung cancer
★ LLC
★ Traditional Chinese Medicine
★ estrogen pathway
★ Connectivity Map
★ Solasodine
論文目次 中文摘要 i
Abstract ii
List of Table vi
List of Figure vii
List of Supplement’s Table viii
List of Supplement’s Figure ix
List of Abbreviation x
1. Introduction 1
1.1 Lung Cancer 1
1.2 Lung Cancer Metastasis and Migration 2
1.3 The Potential of BP010W in Traditional Chinese Medicine 2
1.4 Bioinformatics 2
1.5 Microarray Technology 3
1.6 The Connectivity Map (cMap) 3
1.7 Signalling Transduction Pathway 4
1.8 NF-κB Pathway 4
1.9 Estrogen Signalling Pathway 4
1.10 CD44 Pathway 5
2. Materials and Methods 6
2.1 Cell Culture 6
2.2 Drug Preparation 6
2.3 Wound Healing Assay 6
2.4 Transwell-Assay 6
2.5 Cell Viability Analysis 7
2.6 Microarray Analysis 7
2.7 TAC (Transcriptome Analysis Console) 8
2.8 Function and pathway analysis 8
2.9 L1000 expression profiling data 9
3. Results 10
3.1 BP010W 10
3.1.1 Wound Healing Assay 10
3.1.2 Transcriptome Analysis Console (TAC) 11
3.1.3 Function and Pathway Analysis 16
3.1.4 Singalling Pathways 17
3.1.5 Connectivity Map 18
3.2 Solasodine 25
3.2.1 The Effect of Solasodine on Migration 25
3.2.2 Compounds of BP010W 27
4. Summary and Discussion 31
5. Reference 33
6. Supplements 40
參考文獻 [1] Shegokar R, Sawant S. Cancer research and therapy: Where are we today?. International Journal of Cancer Therapy and Oncology. 2014 October 2(4): 02048. doi: 10.14319/ijcto.0204.8
[2] IARC Press release, 2013. Available from http://ci5.iarc.fr/ [Accessed on May 02, 2014]
[3] Mithoowani H, Febbraro M. Non-Small-Cell Lung Cancer in 2022: A Review for General Practitioners in Oncology. Curr Oncol. 2022 Mar 9;29(3):1828-1839. doi: 10.3390/curroncol29030150. PMID: 35323350; PMCID: PMC8946954.
[4] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.
[4] Luo YH, Chiu CH, Scott Kuo CH, Chou TY, Yeh YC, Hsu HS, Yen SH, Wu YH, Yang JC, Liao BC, Hsia TC, Chen YM. Lung Cancer in Republic of China. J Thorac Oncol. 2021 Apr;16(4):519-527. doi: 10.1016/j.jtho.2020.10.155. PMID: 33781442.
[5] Chang YJ, Huang JY, Lin CH, Wang BY. Survival and Treatment of Lung Cancer in Taiwan between 2010 and 2016. J Clin Med. 2021 Oct 12;10(20):4675. doi: 10.3390/jcm10204675. PMID: 34682798; PMCID: PMC8540538.
[6] Pesch B, Kendzia B, Gustavsson P, Jöckel KH, Johnen G, Pohlabeln H, Olsson A, Ahrens W, Gross IM, Brüske I, Wichmann HE, Merletti F, Richiardi L, Simonato L, Fortes C, Siemiatycki J, Parent ME, Consonni D, Landi MT, Caporaso N, Zaridze D, Cassidy A, Szeszenia-Dabrowska N, Rudnai P, Lissowska J, Stücker I, Fabianova E, Dumitru RS, Bencko V, Foretova L, Janout V, Rudin CM, Brennan P, Boffetta P, Straif K, Brüning T. Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. 2012 Sep 1;131(5):1210-9. doi: 10.1002/ijc.27339. Epub 2011 Dec 14. PMID: 22052329; PMCID: PMC3296911.
[7] Dubin S, Griffin D. Lung Cancer in Non-Smokers. Mo Med. 2020 Jul-Aug;117(4):375-379. PMID: 32848276; PMCID: PMC7431055.
[8] Riudavets M, Garcia de Herreros M, Besse B, Mezquita L. Radon and Lung Cancer: Current Trends and Future Perspectives. Cancers (Basel). 2022 Jun 27;14(13):3142. doi: 10.3390/cancers14133142. PMID: 35804914; PMCID: PMC9264880.
[9] Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7(1):3. doi: 10.1038/s41572-020-00235-0. PMID: 33446664; PMCID: PMC8177722.
[10] Basumallik N, Agarwal M. Small Cell Lung Cancer. [Updated 2022 Jul 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482458/
[11] Raz DJ, Gomez SL, Chang ET, Kim JY, Keegan TH, Pham J, Kukreja J, Hiatt RA, Jablons DM. Epidemiology of non-small cell lung cancer in Asian Americans: incidence patterns among six subgroups by nativity. J Thorac Oncol. 2008 Dec;3(12):1391-7. doi: 10.1097/JTO.0b013e31818ddff7. PMID: 19057262; PMCID: PMC5737739.
[12] Kim J, Lee H, Huang BW. Lung Cancer: Diagnosis, Treatment Principles, and Screening. Am Fam Physician. 2022 May 1;105(5):487-494. PMID: 35559635.
[13] Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med. 2011 Dec;32(4):605-44. doi: 10.1016/j.ccm.2011.09.001. PMID: 22054876; PMCID: PMC3864624.
[14] Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016 Jun;5(3):288-300. doi: 10.21037/tlcr.2016.06.07. PMID: 27413711; PMCID: PMC4931124.
[15] Glatzer M, Schmid S, Radovic M, Früh M, Putora PM. The role of radiation therapy in the management of small cell lung cancer. Breathe (Sheff). 2017 Dec;13(4):e87-e94. doi: 10.1183/20734735.009617. PMID: 29928456; PMCID: PMC6003267.
[16] Amjad MT, Chidharla A, Kasi A. Cancer Chemotherapy. [Updated 2023 Feb 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564367/


[17] Shrestha A, Martin C, Burton M, Walters S, Collins K, Wyld L. Quality of life versus length of life considerations in cancer patients: A systematic literature review. Psychooncology. 2019 Jul;28(7):1367-1380. doi: 10.1002/pon.5054. Epub 2019 May 15. PMID: 30838697; PMCID: PMC6619389.
[18] Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog. 2013;18(1-2):43-73. doi: 10.1615/critrevoncog.v18.i1-2.40. PMID: 23237552; PMCID: PMC3597235.
[19] Leong SP, Naxerova K, Keller L, Pantel K, Witte M. Molecular mechanisms of cancer metastasis via the lymphatic versus the blood vessels. Clin Exp Metastasis. 2022 Feb;39(1):159-179. doi: 10.1007/s10585-021-10120-z. Epub 2021 Nov 12. PMID: 34767139; PMCID: PMC8967809.
[20] Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002 Aug;2(8):563-72. doi: 10.1038/nrc865. PMID: 12154349.
[21] Park HK, Han J, Kwon GY, Yeo MK, Bae GE. Patterns of Extrathoracic Metastasis in Lung Cancer Patients. Curr Oncol. 2022 Nov 16;29(11):8794-8801. doi: 10.3390/curroncol29110691. PMID: 36421344; PMCID: PMC9689009.
[22] Marshall AC. Traditional Chinese Medicine and Clinical Pharmacology. Drug Discovery and Evaluation: Methods in Clinical Pharmacology. 2020 Mar 2:455–82. doi: 10.1007/978-3-319-68864-0_60. PMCID: PMC7356495.
[23] Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX, Chen SJ, Chen Z. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4826-31. doi: 10.1073/pnas.0712365105. Epub 2008 Mar 14. PMID: 18344322; PMCID: PMC2290784.
[24] Xiang ML, Hu BY, Qi ZH, Wang XN, Xie TZ, Wang ZJ, Ma DY, Zeng Q, Luo XD. Chemistry and bioactivities of natural steroidal alkaloids. Nat Prod Bioprospect. 2022 Jun 15;12(1):23. doi: 10.1007/s13659-022-00345-0. PMID: 35701630; PMCID: PMC9198197.

[25] Shen KH, Hung JH, Chang CW, Weng YT, Wu MJ, Chen PS. Solasodine inhibits invasion of human lung cancer cell through downregulation of miR-21 and MMPs expression. Chem Biol Interact. 2017 Apr 25;268:129-135. doi: 10.1016/j.cbi.2017.03.005. Epub 2017 Mar 7. PMID: 28283413.
[26] Bayat A. Science, medicine, and the future: Bioinformatics. BMJ. 2002 Apr 27;324(7344):1018-22. doi: 10.1136/bmj.324.7344.1018. PMID: 11976246; PMCID: PMC1122955.
[27] Trevino V, Falciani F, Barrera-Saldaña HA. DNA microarrays: a powerful genomic tool for biomedical and clinical research. Mol Med. 2007 Sep-Oct;13(9-10):527-41. doi: 10.2119/2006-00107.Trevino. PMID: 17660860; PMCID: PMC1933257.
[28] Govindarajan R, Duraiyan J, Kaliyappan K, Palanisamy M. Microarray and its applications. J Pharm Bioallied Sci. 2012 Aug;4(Suppl 2):S310-2. doi: 10.4103/0975-7406.100283. PMID: 23066278; PMCID: PMC3467903.
[29] Li X, Gu W, Mohan S, Baylink DJ. DNA microarrays: their use and misuse. Microcirculation. 2002 Jan;9(1):13-22. doi: 10.1038/sj.mn.7800118. PMID: 11896556.
[30] Tarca AL, Romero R, Draghici S. Analysis of microarray experiments of gene expression profiling. Am J Obstet Gynecol. 2006 Aug;195(2):373-88. doi: 10.1016/j.ajog.2006.07.001. PMID: 16890548; PMCID: PMC2435252.
[31] Heller MJ. DNA microarray technology: devices, systems, and applications. Annu Rev Biomed Eng. 2002;4:129-53. doi: 10.1146/annurev.bioeng.4.020702.153438. Epub 2002 Mar 22. PMID: 12117754.
[32] Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, Reich M, Hieronymus H, Wei G, Armstrong SA, Haggarty SJ, Clemons PA, Wei R, Carr SA, Lander ES, Golub TR. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006 Sep 29;313(5795):1929-35. doi: 10.1126/science.1132939. PMID: 17008526.



[33] Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK, Lahr DL, Hirschman JE, Liu Z, Donahue M, Julian B, Khan M, Wadden D, Smith IC, Lam D, Liberzon A, Toder C, Bagul M, Orzechowski M, Enache OM, Piccioni F, Johnson SA, Lyons NJ, Berger AH, Shamji AF, Brooks AN, Vrcic A, Flynn C, Rosains J, Takeda DY, Hu R, Davison D, Lamb J, Ardlie K, Hogstrom L, Greenside P, Gray NS, Clemons PA, Silver S, Wu X, Zhao WN, Read-Button W, Wu X, Haggarty SJ, Ronco LV, Boehm JS, Schreiber SL, Doench JG, Bittker JA, Root DE, Wong B, Golub TR. A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles. Cell. 2017 Nov 30;171(6):1437-1452.e17. doi: 10.1016/j.cell.2017.10.049. PMID: 29195078; PMCID: PMC5990023.
[34] Mousavi SZ, Rahmanian M, Sami A. A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection. Infect Genet Evol. 2020 Dec;86:104610. doi: 10.1016/j.meegid.2020.104610. Epub 2020 Oct 29. PMID: 33130005; PMCID: PMC7598903.
[35] Musa A, Ghoraie LS, Zhang SD, Glazko G, Yli-Harja O, Dehmer M, Haibe-Kains B, Emmert-Streib F. A review of connectivity map and computational approaches in pharmacogenomics. Brief Bioinform. 2018 May 1;19(3):506-523. doi: 10.1093/bib/bbw112. Erratum in: Brief Bioinform. 2017 Sep 1;18(5):903. PMID: 28069634; PMCID: PMC5952941.
[36] Wu D, Pepowski B, Takahashi S, Kron SJ. A cMap-enabled gene expression signature-matching approach identifies small-molecule inducers of accelerated cell senescence. BMC Genomics. 2019 Apr 15;20(1):290. doi: 10.1186/s12864-019-5653-x. PMID: 30987592; PMCID: PMC6466706.
[37] Iwata M, Yamanishi Y. The Use of Large-Scale Chemically-Induced Transcriptome Data Acquired from LINCS to Study Small Molecules. Methods Mol Biol. 2019;1888:189-203. doi: 10.1007/978-1-4939-8891-4_11. PMID: 30519948.
[38] Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med. 2015 Apr 1;5(4):a006098. doi: 10.1101/cshperspect.a006098. PMID: 25833940; PMCID: PMC4382731.
[39] Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Cell Surface Receptors and Their Signal Transduction Pathways. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10043/
[40] Liu T, Zhang L, Joo D, Sun SC. NF-κB signalling in inflammation. Signal Transduct Target Ther. 2017;2:17023–. doi: 10.1038/sigtrans.2017.23. Epub 2017 Jul 14. PMID: 29158945; PMCID: PMC5661633.
[41] Zhang T, Ma C, Zhang Z, Zhang H, Hu H. NF-κB signalling in inflammation and cancer. MedComm (2020). 2021 Dec 16;2(4):618-653. doi: 10.1002/mco2.104. PMID: 34977871; PMCID: PMC8706767.
[42] Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res. 2014 Sep;2(9):823-30. doi: 10.1158/2326-6066.CIR-14-0112. PMID: 25187272; PMCID: PMC4155602.
[43] Hayden MS, Ghosh S. Signalling to NF-kappaB. Genes Dev. 2004 Sep 15;18(18):2195-224. doi: 10.1101/gad.1228704. PMID: 15371334.
[44] Fuentes N, Silveyra P. Estrogen receptor signalling mechanisms. Adv Protein Chem Struct Biol. 2019;116:135-170. doi: 10.1016/bs.apcsb.2019.01.001. Epub 2019 Feb 4. PMID: 31036290; PMCID: PMC6533072.
[45] Li Y, Wang JP, Santen RJ, Kim TH, Park H, Fan P, Yue W. Estrogen stimulation of cell migration involves multiple signalling pathway interactions. Endocrinology. 2010 Nov;151(11):5146-56. doi: 10.1210/en.2009-1506. Epub 2010 Sep 22. PMID: 20861240; PMCID: PMC2954727.
[46] Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT, Horwitz AF. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol. 2004 Feb;6(2):154-61. doi: 10.1038/ncb1094. Epub 2004 Jan 25. PMID: 14743221.
[47] Singleton PA, Bourguignon LY. CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signalling leading to nitric oxide production and endothelial cell adhesion and proliferation. Exp Cell Res. 2004 Apr 15;295(1):102-18. doi: 10.1016/j.yexcr.2003.12.025. PMID: 15051494.
[48] Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018 May 10;11(1):64. doi: 10.1186/s13045-018-0605-5. PMID: 29747682; PMCID: PMC5946470.


[49] Wang YY, Vadhan A, Chen PH, Lee YL, Chao CY, Cheng KH, Chang YC, Hu SC, Yuan SF. CD44 Promotes Lung Cancer Cell Metastasis through ERK-ZEB1 Signalling. Cancers (Basel). 2021 Aug 12;13(16):4057. doi: 10.3390/cancers13164057. PMID: 34439211; PMCID: PMC8392539.
[50] Zhao L, Huang S, Mei S, Yang Z, Xu L, Zhou N, Yang Q, Shen Q, Wang W, Le X, Lau WB, Lau B, Wang X, Yi T, Zhao X, Wei Y, Warner M, Gustafsson JÅ, Zhou S. Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis. Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3673-E3681. doi: 10.1073/pnas.1803291115. Epub 2018 Mar 28. PMID: 29592953; PMCID: PMC5910874
指導教授 蘇立仁 吳立青(Li-Jen Su Li-Ching Wu) 審核日期 2023-6-28
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