How many passages usually need to develop drug resistance for this cell line by two drugs? Could you let me know the cell response to these drugs?
1. Cisplatin
2. 5-FU
Investigation of the role of p53 in chemotherapy resistance of lung cancer cell lines.
Breen L1, Heenan M, Amberger-Murphy V, Clynes M.
Abstract
BACKGROUND:
p53 is a tumour suppressor gene, which is mutated in more than half of all tumours. Most chemotherapeutic drugs cause DNA damage, which is sensed by p53; the cell can then try to repair the damage or induce cell suicide. If the p53 machinery is defective, effective chemotherapy is made more difficult.
MATERIALS AND METHODS:
Wild-type p53 was transfected into lung cancer cell lines with different p53 status. The transfected cells were tested for changes in sensitivity to a range of chemotherapeutic agents.
RESULTS:
We observed only modest changes in the sensitivity to the chemotherapeutic agents adriamycin, taxol and carboplatin in the transfected cells lines. p53 protein was detected in a transfected clone of the cell line H1299, whose parent cells are p53 null. However, the protein did not accumulate after DNA damage, suggesting that this cell line utilises alternative pathways for responding to stress, and no longer has a functional p53 pathway.
CONCLUSION:
The results suggest that introduction of wild-type p53 alone is not sufficient to substantially alter the sensitivity of a cell line to a given chemotherapeutic agent.
https://www.ncbi.nlm.nih.gov/pubmed/17593631
Thank you very much, Mr. Aldallal. I am treating TP53 cell line with Cisplatin 2 micromolar and 5-FU 1 micromolar. IC50 value for Cisplatin increased by 80%. This indicates TP53 cell (p53 protein mutated) is developing an alternate mechanism for responding DNA damage drug. While p53 protein is not tested yet. Thanks
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