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研究生:曾涵郁
研究生(外文):Han Yu Tseng
論文名稱:研究WDR5抑制劑WDR5-0103以及酪胺酸激酶抑制劑Lazertinib對於過度表現ABCB1或ABCG2之多重抗藥性癌細胞的增敏作用
論文名稱(外文):Investigating the chemosensitization effect of WDR5 inhibitor WDR5-0103 and EGFR inhibitor lazertinib on ABCB1- or ABCG2-overexpressing multidrug-resistant cancer cells
指導教授:吳宗圃
指導教授(外文):C. P. Wu
學位類別:碩士
校院名稱:長庚大學
系所名稱:生物醫學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2022
畢業學年度:110
語文別:中文
論文頁數:120
中文關鍵詞:癌症多重抗藥性ABC轉運蛋白LazertinibWDR5-0103
外文關鍵詞:cancermultidrug resistanceABC transporterLazertinibWDR5-0103
相關次數:
  • 被引用被引用:0
  • 點閱點閱:37
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  • 下載下載:0
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目錄
摘要 i
ABSTRACT iii
目錄 iv
圖目錄 vi
附錄目錄 ix
緒論 - 1 -
癌症 (Cancer) - 2 -
多重抗藥性 (Multidrug resistance) - 3 -
ATP-binding cassette (ABC) transporter - 4 -
ABCB1 (P-glycoprotein; MDR1) - 5 -
ABCG2 ( ABCP; BCRP; MXR ) - 6 -
WDR5-0103 - 7 -
Lazertinib (YH25448,GNS-1480) - 8 -
研究動機 - 10 -
材料與方法 - 12 -
實驗藥物與細胞培養材料 - 12 -
細胞培養(Cell culture) - 12 -
細胞存活率分析 (MTT Assay) - 15 -
細胞存活率分析 (CCK-8) - 16 -
Flow cytometry - 17 -
西方墨點法 (Western blot) - 18 -
細胞凋亡測定 (Apoptosis assay) - 20 -
量化和統計分析 - 22 -
Results - 23 -
WDR5-0103和lazertinib對細胞毒性的測試 - 23 -
WDR5-0103和lazertinib回復過度表現ABCB1的藥物敏感度能力 - 23 -
WDR5-0103和lazertinib回復過度表現ABCG2的藥物敏感度能力 - 24 -
WDR5-0103和lazertinib誘導細胞凋亡 - 25 -
WDR5-0103和lazertinib不影響ABC transporters蛋白量 - 27 -
WDR5-0103和lazertinib在ABC transporters的功能性測試 - 28 -
Discussion and Conclusion - 30 -
參考資料 - 37 -
圖表 - 43 -
附錄 - 91 -

圖目錄
Figure 1. WDR5-0103對各細胞系的毒性測試 - 43 -
Figure 2. WDR5-0103恢復過度表現ABCB1的細胞對ABCB1受質藥物paclitaxel的敏感性 - 45 -
Figure 3. WDR5-0103恢復過度表現ABCB1的細胞對ABCB1受質藥物colchicine的敏感性 - 47 -
Figure 4. WDR5-0103恢復過度表現ABCB1的細胞對ABCB1受質藥物vincristine的敏感性 - 49 -
Figure 5. WDR5-0103恢復過度表現ABCG2的細胞對ABCG2受質藥物mitoxantrone的敏感性 - 51 -
Figure 6. WDR5-0103恢復過度表現ABCG2的細胞對ABCG2受質藥物topotecan的敏感性 - 53 -
Figure 7. WDR5-0103恢復過度表現ABCG2的細胞對ABCG2受質藥物SN-38的敏感性 - 55 -
Figure 8. WDR5-0103使KB-V1細胞株對colchicine所誘導之細胞凋亡及S1-MI-80細胞株對topotecan所誘導之細胞凋亡重新感到敏感 - 58 -
Figure 9. WDR5-0103對KB-3-1和KB-V1蛋白質ABCB1表現量之影響 - 59 -
Figure 10. WDR5-0103對OVCAR-8和NCI-ADR-RES蛋白質ABCB1表現量之影響 - 60 -
Figure 11. . WDR5-0103對H460和H460- MX20蛋白質ABCG2表現量之影響 - 61 -
Figure 12. WDR5-0103對S1和S1-MI-80蛋白質ABCG2表現量之影響 - 62 -
Figure 13. WDR5-0103對ABCB1功能性之影響 - 64 -
Figure 14. WDR5-0103對ABCG2功能性之影響 - 66 -
Figure 15. Lazertinib對各細胞系的毒性測試 - 67 -
Figure 16. Lazertinib恢復過度表現ABCB1的細胞對ABCB1受質藥物paclitaxel的敏感性 - 69 -
Figure 17. Lazertinib恢復過度表現ABCB1的細胞對ABCB1受質藥物colchicine的敏感性 - 71 -
Figure 18. Lazertinib恢復過度表現ABCB1的細胞對ABCB1受質藥物vincristine的敏感性 - 73 -
Figure 19. Lazertinib恢復過度表現ABCG2的細胞對ABCG2受質藥物mitoxantrone的敏感性 - 75 -
Figure 20. Lazertinib恢復過度表現ABCG2的細胞對ABCG2受質藥物topotecan的敏感性 - 77 -
Figure 21. Lazertinib恢復過度表現ABCG2的細胞對ABCG2受質藥物SN-38的敏感性 - 79 -
Figure 22. Lazertinib使KB-V1細胞株對colchicine所誘導之細胞凋亡及S1-MI-80細胞株對topotecan所誘導之細胞凋亡重新感到敏感 - 82 -
Figure 23. Lazertinib對KB-3-1和KB-V1蛋白質ABCB1表現量之影響 - 83 -
Figure 24. Lazertinib對OVCAR-8和NCI-ADR-RES蛋白質ABCB1表現量之影響 - 84 -
Figure 25. Lazertinib對H40和H460-MX20蛋白質ABCG2表現量之影響 - 85 -
Figure 26. Lazertinib對S1和S1-MI-80蛋白質ABCG2表現量之影響 - 86 -
Figure 27. Lazertinib對ABCB1功能性之影響 - 88 -
Figure 28. Lazertinib對ABCG2功能性之影響 - 90 -
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