Mechanisms associated with cell adhesion mediated-drug resistance (CAM-DR) in high-and low-metastatic nasopharyngeal carcinoma cells

Name: Utapin Ngaokrajang

LCSH: Kasetsart University -- Theses. M.S. (Biochemistry) 2021

Classification :.LCCS: RC280.P4

LCSH: Kasetsart University. -- Department of Biochemistry -- Theses

LCSH: Nasopharyngeal carcinoma

LCSH: Nasopharynx -- Cancer

LCSH: Cell adhesion

LCSH: Drug carriers (Pharmacy)

Abstract: Nasopharyngeal carcinoma (NPC) is commonly found in Southeast Asian countries including Thailand. A failure in the treatment is mainly due to a resistance to anti-cancer drugs including cisplatin. In this research, we aim to investigate the mechanisms of cell adhesion mediated drug resistance (CAM-DR) in NPC using an in vitro 3D multicellular tumor spheroid (MCTS) model. To begin with, we established the 3D MCTS of high- (5-8F) and low- (6-10B) metastatic NPC cells where cell-cell and cell-extracellular matrix interactions were enhanced. Also, cisplatin-resistant 5-8F (5-8FcisR) and 6-10B (6-10BcisR) were developed and confirmed by the resistant index of 5.52 and 3.32 folds, respectively. Morphological alteration and retarded cell proliferation of the 3D NPC and NPC cisR cells were observed. However, their cell cycles revealed to be indifferent compared with their parental cells. For gene and protein expressions, integrin α5 and β1 were significantly upregulated in both 2D NPC cisR, 3D NPC and 3D NPC cisR. Their upregulations correlated with higher resistance to cisplatin. The degree of apoptosis was decreased, likely through an inactivation of caspase-3. Additionally, the 3D NPC cisR showed reduced migratory properties. Furthermore, the immunofluorescence staining showed that NPC cisR cells exhibited significantly higher integrin α5 and β1 intensities than their parental cells. To confirm the contribution of integrin α5 and β1 to the cisplatin susceptibility, an integrin inhibitor ATN-161 were treated with both 2D and 3D NPC cells. Western blot analysis displayed a significant decrease in the integrin α5 and β1 expression. The treated cells also demonstrated dramatic reduction in resistant index. In conclusion, the mechanism of CAM-DR in NPC is involved in the overexpression of integrin α5β1 which can be employed as a potential target for NPC treatment.

Kasetsart University. Office of the University Library

Address: Bangkok

Email: tdckulib@ku.ac.th

Name: Pichamon Kiatwuthinon

Role: Thesis Advisor

Name: Nattanan T-Thienprasert

Role: Thesis CO-Advisor

Created: 2021

Modified: 2025-07-11

Issued: 2025-07-11

วิทยานิพนธ์/Thesis

application/pdf

URL: https://www.lib.ku.ac.th/KUthesis/2564/utapin-nga-all.pdf

CallNumber: RC280.P4 .U83

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Biochemistry

Grantor: Kasetsart University

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