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Upregulation of MDR- and EMT-Related Molecules in Cisplatin-Resistant Human Oral Squamous Cell Carcinoma Cell Lines.

Authors
  • Choi, Hyeong Sim1
  • Kim, Young-Kyun2
  • Yun, Pil-Young3
  • 1 Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, 82 Gumi-ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Korea. [email protected] , (North Korea)
  • 2 Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, 82 Gumi-ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Korea. [email protected] , (North Korea)
  • 3 Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, 82 Gumi-ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Korea. [email protected] , (North Korea)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Jun 21, 2019
Volume
20
Issue
12
Identifiers
DOI: 10.3390/ijms20123034
PMID: 31234332
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cisplatin is one of the major drugs used in oral cancer treatments, but its usage can be limited by acquired drug resistance. In this study, we established three cisplatin-resistant oral squamous cell carcinoma (OSCC) cell lines and characterized them using cell viability assays, qPCR, Western blotting, FACS, immunofluorescence, and wound healing assays. Three OSCC cell lines (YD-8, YD-9, and YD-38) underwent long-term exposure to cisplatin, eventually acquiring resistance to the drug, which was confirmed by an MTT assay. In these three newly established cell lines (YD-8/CIS, YD-9/CIS, and YD-38/CIS), overexpression of multidrug resistance (MDR)-related genes was detected by qPCR and Western blotting. The cell lines displayed an increase in the functional activities of breast cancer resistance protein (BCRP) and multidrug resistance protein1 (MDR1) by rhodamine 123 and bodipy FL prazosin accumulation assays. Moreover, the cisplatin-resistant cells underwent morphological changes, from round to spindle-shaped, increased expression of epithelial-to-mesenchymal transition (EMT)-related molecules such as N-cadherin, and showed increased cell migration when compared with the parental cell lines. These results suggest that these newly established cell lines have acquired drug resistance and EMT induction.

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