Assessing the Anti-Metastatic Effects of Triptonide, for a More Efficient Treatment of Triple Negative Basal-Like Breast Cancer, Using a Novel Disease Model Danio rerio
General Material Designation
[Thesis]
First Statement of Responsibility
Harb, Jerry
Subsequent Statement of Responsibility
Hao, Jijun
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
Western University of Health Sciences
Date of Publication, Distribution, etc.
2019
GENERAL NOTES
Text of Note
76 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
M.S.B.S.
Body granting the degree
Western University of Health Sciences
Text preceding or following the note
2019
SUMMARY OR ABSTRACT
Text of Note
The majority of cancer related deaths are a consequence of metastasis to tissues and organs beyond the primary site of tumorigenesis. Basal-like breast cancer (BLBC) is an aggressive molecular subtype that results in poor clinical outcome of patients, where the patient's mortality occurs within a shorter median time than that of other breast cancer types. Current therapeutic methods, such as surgery, radiation, and chemotherapy, pose a number of disadvantages with selective targeting, cytotoxic effects, and complete elimination of abnormal cells. In comparison, novel treatments of crucial regulatory pathways in cancer progression may offer a more selective targeting mechanism. It has been observed that dysregulation of the Wnt and Hedgehog (Hh) pathways play a role in tumorigenesis in triple negative basal-like breast cancer. Mediating signal dysfunction in the Wnt and Hedgehog pathways to restore normal cell physiology, and in turn localizing cancerous tumor cells to the primary site is important in the potential treatment of these aggressive cancers. While traditional cancer research has utilized the murine model, novel organismal systems have emerged that circumvent difficulties researchers face using current in-vivo disease models. Danio rerio, or the zebrafish is a promising model for cancer research. We employed an optically transparent transgenic model of zebrafish known as the Casper zebrafish to visualize cancer cell migration. In addition, we investigated the application of key bioactive compound, triptonide, isolated from Triptegyrium wilfordii, to inhibit metastasis in-vitro and in-vivo, and its potential as a more efficient strategy of cancer therapy. We demonstrated anti-proliferative effects of triptonide on triple negative breast cancer line BT549, in-vitro and in-vivo, and reduced metastatic invasiveness in-vivo in the zebrafish model.