File Download
Supplementary
-
Citations:
- Appears in Collections:
postgraduate thesis: Study of ginsenoside compound K on epithelial-mesenchymal transition and cancer stemness
Title | Study of ginsenoside compound K on epithelial-mesenchymal transition and cancer stemness |
---|---|
Authors | |
Advisors | Advisor(s):Wong, AST |
Issue Date | 2018 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Deng, S. [鄧珊]. (2018). Study of ginsenoside compound K on epithelial-mesenchymal transition and cancer stemness. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Cancer stem cells (CSCs) are a subpopulation of tumor cells that exhibit self-renewal and differentiation capacity. CSCs play a crucial role in cancer initiation, progression, and therapy resistance. Epithelial-to-mesenchymal transition (EMT) is a highly conserved cellular process that contributes to cancer progression, including cancer metastasis, therapy resistance and disease recurrence. During tumor metastasis, cells undergo EMT, acquiring mesenchymal features, migrating to other tissues or vessels. Recent studies also have linked the EMT process to CSC formation. These findings suggest that CSCs and EMT are closely correlated with cancer recurrence and metastasis. In this study, the roles of ginsenoside compound K (CK) on EMT and CSC properties were investigated in two cancer models, ovarian and colon cancers, which are two highly metastatic cancer types. In ovarian cancer cells, CK exhibited potent cytotoxicity on CSCs, it effectively suppressed CSC self-renewal without regrowth, sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These actions of CK were correlated with Wnt/β-catenin signaling pathway through inhibiting β-catenin/T-cell factor-dependent transcription and its targeted drug transporter genes ABCG2 and P-glycoprotein. This study also identified reversal of EMT as a new player in CK-mediated inhibition of CSCs. In xenograft tumor model, CK treatment inhibited CSCs growth and self-renewal with no observed toxicity in normal tissues. These results demonstrate that CK can be further studied as a nutraceutical prototype in refractory tumors treatment. In colon cancer cells, CK treatment significantly downregulated the expression of Nur77 signaling in a dose-dependent manner, and inhibited Nur77-induced CSC phenotype and EMT.
These effects were mediated through Nur77/Akt signaling pathway. PIK3CA was the target of this process to inhibit Akt expression. This study also identified microRNA let-7i-5p as a cancer suppressor gene in the Nur77-mediated PIK3CA regulation and overexpressed let-7i-5p could reduce the increased expression of PIK3CA and Akt. These findings demonstrated that Nur77 should be considered as a new regulatory target in cancer drug treatment. Collectively, this study provides important insights in CK on CSC and EMT properties, and uncovers the important roles of Nur77 in hypoxia-induced EMT, that would help to design a novel therapeutic strategy.
|
Degree | Doctor of Philosophy |
Subject | Ginseng - Therapeutic use Transforming growth factors Cancer cells |
Dept/Program | Biological Sciences |
Persistent Identifier | http://hdl.handle.net/10722/267742 |
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Wong, AST | - |
dc.contributor.author | Deng, Shan | - |
dc.contributor.author | 鄧珊 | - |
dc.date.accessioned | 2019-03-01T03:44:41Z | - |
dc.date.available | 2019-03-01T03:44:41Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Deng, S. [鄧珊]. (2018). Study of ginsenoside compound K on epithelial-mesenchymal transition and cancer stemness. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/267742 | - |
dc.description.abstract | Cancer stem cells (CSCs) are a subpopulation of tumor cells that exhibit self-renewal and differentiation capacity. CSCs play a crucial role in cancer initiation, progression, and therapy resistance. Epithelial-to-mesenchymal transition (EMT) is a highly conserved cellular process that contributes to cancer progression, including cancer metastasis, therapy resistance and disease recurrence. During tumor metastasis, cells undergo EMT, acquiring mesenchymal features, migrating to other tissues or vessels. Recent studies also have linked the EMT process to CSC formation. These findings suggest that CSCs and EMT are closely correlated with cancer recurrence and metastasis. In this study, the roles of ginsenoside compound K (CK) on EMT and CSC properties were investigated in two cancer models, ovarian and colon cancers, which are two highly metastatic cancer types. In ovarian cancer cells, CK exhibited potent cytotoxicity on CSCs, it effectively suppressed CSC self-renewal without regrowth, sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These actions of CK were correlated with Wnt/β-catenin signaling pathway through inhibiting β-catenin/T-cell factor-dependent transcription and its targeted drug transporter genes ABCG2 and P-glycoprotein. This study also identified reversal of EMT as a new player in CK-mediated inhibition of CSCs. In xenograft tumor model, CK treatment inhibited CSCs growth and self-renewal with no observed toxicity in normal tissues. These results demonstrate that CK can be further studied as a nutraceutical prototype in refractory tumors treatment. In colon cancer cells, CK treatment significantly downregulated the expression of Nur77 signaling in a dose-dependent manner, and inhibited Nur77-induced CSC phenotype and EMT. These effects were mediated through Nur77/Akt signaling pathway. PIK3CA was the target of this process to inhibit Akt expression. This study also identified microRNA let-7i-5p as a cancer suppressor gene in the Nur77-mediated PIK3CA regulation and overexpressed let-7i-5p could reduce the increased expression of PIK3CA and Akt. These findings demonstrated that Nur77 should be considered as a new regulatory target in cancer drug treatment. Collectively, this study provides important insights in CK on CSC and EMT properties, and uncovers the important roles of Nur77 in hypoxia-induced EMT, that would help to design a novel therapeutic strategy. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Ginseng - Therapeutic use | - |
dc.subject.lcsh | Transforming growth factors | - |
dc.subject.lcsh | Cancer cells | - |
dc.title | Study of ginsenoside compound K on epithelial-mesenchymal transition and cancer stemness | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Doctor of Philosophy | - |
dc.description.thesislevel | Doctoral | - |
dc.description.thesisdiscipline | Biological Sciences | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_991044081529103414 | - |
dc.date.hkucongregation | 2019 | - |
dc.identifier.mmsid | 991044081529103414 | - |