Optimisation of a selection strategy for drug resistance osteosarcoma cell lines

Low, Kaan, Hills, Frank ORCID logoORCID: https://orcid.org/0000-0001-8235-7545, Roberts, Helen C. ORCID logoORCID: https://orcid.org/0000-0003-1974-0319 and Stordal, Britta K. ORCID logoORCID: https://orcid.org/0000-0002-7892-951X (2018) Optimisation of a selection strategy for drug resistance osteosarcoma cell lines. In: Research Degrees Students' Summer Conference, 04 Sept 2018, Middlesex University, London, UK. . [Conference or Workshop Item]

Abstract

Osteosarcoma is the most common primary malignant bone tumour and also the second highest cause of cancer related death in children and teenagers. The treatment of osteosarcoma including the use of neo-adjuvant chemotherapy in combination with surgery has increased the long-term survival rate of patients in last few decades. The most effective anticancer drug used against osteosarcoma are cisplatin, doxorubicin and high-dose methotrexate. The cure rate of osteosarcoma by surgery ranges from 15% to 20% and improves dramatically to 70% in the combination with chemotherapy. However, additional chemotherapy is palliative and toxic to approximately 40% of the patients with progression of osteosarcoma after front-line therapy. The aim of this study is to establish new drug-resistant osteosarcoma cell lines and investigate their mechanism of resistance. The human osteosarcoma cell lines MG-63 and HOS-143b will be treated with cisplatin, methotrexate and doxorubicin. The cell lines will expose to clinically relevant doses in the medium to select for the drug-resistant sublines. The morphological features of the drug-resistant subline will be observed using inverted microscopy. The growth rate of the developing drug-resistant sublines of MG-63 and HOS-143b will be calculated using an Image J method for determining cell confluence. The IC50s of each drug will be established in each cell line to optimise the doses used to treat the parental cell lines. The medium condition of MG-63 and HOS-143b is being optimised to mimic the clinical situation by removing antibiotic for both cell lines and bromodeoxyuridine (BrDU) for HOS143b.The growth rate of MG-63 and HOS-143b has been calculated and the doubling time is 34.15 ± 7.707 and 24.6 hours respectively. The Image J method for cell confluence has been optimised and shows a strong correlation to manual cell counts for each cell line. The correlation of Area Fraction and cell count for MG-63 is r=0.9823, which is significant with p value = 0.0005. For HOS-143b, the correlation is r=0.9823, which is also significant with p value = 0.0234. The expected outcome of this study is the establishment of drug-resistant sublines from MG-63 and HOS-143b. The drug-resistant sublines from MG-63 and HOS-143b will obtain a higher fold of resistant to their respective drugs in comparison with their parental cell lines and may also exhibit crossresistance to other drugs. These resistant sublines will be invaluable tools with which to study the resistance of anticancer drugs and to identify the methods to overcome resistance.

Item Type: Conference or Workshop Item (Presentation)
Sustainable Development Goals:
Theme:
Research Areas: A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
Item ID: 35490
Useful Links:
Depositing User: Dr Britta Stordal
Date Deposited: 25 Jul 2022 17:22
Last Modified: 25 Jul 2022 17:33
URI: https://eprints.mdx.ac.uk/id/eprint/35490

Actions (login required)

View Item View Item

Statistics

Activity Overview
6 month trend
0Downloads
6 month trend
0Hits

Additional statistics are available via IRStats2.