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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉興華(Shing-Hwa Liu) | |
| dc.contributor.author | Chia-Hung Wu | en |
| dc.contributor.author | 吳佳鴻 | zh_TW |
| dc.date.accessioned | 2021-06-07T23:52:18Z | - |
| dc.date.copyright | 2020-09-04 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16988 | - |
| dc.description.abstract | 糖尿病在現今社會當中是常見的慢性疾病，根據國際糖尿病聯合會的預估，在2045年時約有7億的人會得到糖尿病。糖尿病會引發一些併發症像是眼睛病變、心血管疾病、腎臟病變以及可能會增加得到癌症的風險。有許多的流行病學統計指出糖尿病會提高得到癌症的風險並且有實驗證明在糖尿病患者體內較一般人含有較多的糖化最終產物也發現會促進癌症的增生及轉移。雖然已有研究證明糖尿病和癌症的正相關性，不過卻很少有研究去探討糖尿病與骨癌之間的關聯，因此想了解糖化最終產物是否會促進骨癌的惡化。在本實驗所使用的細胞為人類骨肉瘤MG63細胞以及人類軟骨肉瘤JJ012細胞，實驗結果發現雖然糖化最終產物Nε-carboxymethyllysine (CML)並不會影響到骨癌細胞的存活率，不過卻會增加骨癌細胞在懸浮生長形成球體的數目(MG63)或面積(JJ012)而且糖化最終產物的受體(RAGE)以及與癌幹細胞有相關的基因MRP1、MDR1、CD44、ALDH1A1以及NANOG的蛋白表現量以及mRNA的表現量有顯著增加；除此之外，在transwell的實驗中發現CML也會增加骨癌細胞轉移以及侵入的數量，由以上的實驗得知，CML會促進骨癌細胞的惡化情形。 | zh_TW |
| dc.description.abstract | Diabetes mellitus is now common disease with critical impacts on human health. According to the International Diabetes Federation, approximately 700 million people will get diabetes by 2045. Also, diabetes mellitus can cause many complications such as eye disease, cardiovascular disease, kidney failure and cancer. The association of diabetes mellitus and an increased cancer risk have been demonstrated from numerous epidemiological studies. Advanced glycation end products have been investigated to promote proliferation, tumorigenesis and metastasis of cancer cells. Despite there is an evidence of positive correlation between diabetes mellitus and cancer risk, much less attention is paid to link between diabetes mellitus and bone cancer. Therefore, we investigated the role of advanced glycation end products in bone cancer cells. The osteosarcoma, MG63 cells and chondrosarcoma, JJ012 cells were used in this study. Although Nε-carboxymethyllysine (CML) would not change the cell viability in bone cancer cells in a dose-dependent manner (0-100 μM) and time-dependent manner (24-72 h), but increase the sphere number of MG63 cells and the area of JJ012 cells. Also, CML would increase the protein expression of receptor for advanced glycation end products (RAGE) and cancer-stemness associated protein like MRP1, MDR1, CD44, ALDH1A1, and NANOG. Furthermore, in transwell migration and invasion assay, CML could increase the cell migration and invasion numbers and increase the protein expression of epithelial-mesenchymal transition markers in MG63 cells and JJ012 cells. As a result, CML could promote the malignancy of bone cancer cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T23:52:18Z (GMT). No. of bitstreams: 1 U0001-0708202023002900.pdf: 3284480 bytes, checksum: 020a7547418d639571716c6dcdafe27f (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 口試委員會審定書 i 誌謝 v 中文摘要 vi Abstract vii List of abbreviation ix Part 1: Introduction 1 1.1 Diabetes mellitus (DM) 1 1.2 Cancer 1 1.3 Bone cancer 4 1.4 Advanced glycation end products (AGEs) 5 1.5 Cancer stem cell 7 Part 2: Aims 9 Part 3: Materials and methods 10 3.1 Cell culture 10 3.2 Establishment of cisplatin-resistant osteosarcoma and chondrosarcoma cell lines 10 3.3 Cell viability assay 11 3.4 Sarcosphere formation assay 11 3.5 Transwell migration and invasion assay 12 3.6 Protein extraction and Western blot analysis 12 3.7 Real time PCR (qPCR) 13 3.8 Statistics 14 Part 4: Results 16 4.1 CML doesn’t change the cell viability but increases the sphere numbers or area in bone cancer cells. 16 4.2 CML increases the protein expression or relative mRNA expression of RAGE, p-NFκB and the expression of cancer-stemness markers in bone cancer cells. 16 4.3 CML increases the numbers of cell migration and invasion in bone cancer cells and impacts the protein expression of epithelial-mesenchymal transition markers. 17 4.4 CML decreases the protein expression of p-AKT or p-GSK3α/β in bone cancer cells. 18 Part 5: Discussion 21 Part 6: Conclusion 25 Part 7: References 26 Part 8: Figures and figure legends 35 Figure 1. CML doesn’t impact the cell viability in bone cancer cells. 35 Figure 2. CML increases the sphere numbers or area in bone cancer cells. 36 Figure 3. CML increases the protein expression of RAGE in bone cancer cells. 37 Figure 4. CML increases the protein expression of cancer-stemness markers in bone cancer cells. 39 Figure 5. CML increases the mRNA expression of cancer-stemness markers in bone cancer cells. 41 Figure 6. CML increases the cell migration in bone cancer cells. 43 Figure 7. CML increases the cell invasion in bone cancer cells. 45 Figure 8. CML impacts the protein expression of EMT markers in bone cancer cells. 47 Figure 9. CML could decrease the protein expression of p-AKT and p-GSK3α/β in bone cancer cells. 49 Figure 10. Establishment of cisplatin-resistant osteosarcoma MG63 cells and chondrosarcoma JJ012 cells. 51 Figure 11. CML doesn’t impact the protein expression of SIRT family in bone cancer cells. 53 Figure 12. ALT-711 could reverse the increased protein expression of RAGE and cancer-stemness markers caused by CML in MG63 cells. 55 | |
| dc.language.iso | zh-TW | |
| dc.subject | 糖化最終產物 | zh_TW |
| dc.subject | 癌幹細胞 | zh_TW |
| dc.subject | 糖化最終產物受體 | zh_TW |
| dc.subject | 糖尿病 | zh_TW |
| dc.subject | 骨癌 | zh_TW |
| dc.subject | bone cancer | en |
| dc.subject | cancer stem cells | en |
| dc.subject | advanced glycation end products | en |
| dc.subject | diabetes mellitus | en |
| dc.subject | receptor for advanced glycation end products | en |
| dc.title | 探討糖化最終產物羧甲基離氨基酸促進骨癌之惡性及其機制 | zh_TW |
| dc.title | Advanced Glycation End Product Nε-carboxymethyllysine Exerts Malignancy on Bone Tumors via the Activation of Skeletal Cancer Stemness | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.author-orcid | 0021-0002-4463-9962 | |
| dc.contributor.advisor-orcid | 劉興華(0023-0054-8562-9842) | |
| dc.contributor.oralexamcommittee | 姜至剛(Chih-Kang Chiang),許美鈴(Meei-Ling Sheu),吳鎮天(Cheng-Tien Wu) | |
| dc.contributor.oralexamcommittee-orcid | 姜至剛(5627-5632-8951-9356),許美鈴(5678-8765-5524-9988),吳鎮天(2345-5422-5565-6656) | |
| dc.subject.keyword | 糖尿病,糖化最終產物,糖化最終產物受體,骨癌,癌幹細胞, | zh_TW |
| dc.subject.keyword | diabetes mellitus,advanced glycation end products,receptor for advanced glycation end products,bone cancer,cancer stem cells, | en |
| dc.relation.page | 55 | |
| dc.identifier.doi | 10.6342/NTU202002672 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-08-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
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