I am assaying cytotoxic activity of some lipid compounds in MDA BD 231 cell line and found cell are showing resistance after treating some compounds. Now I am planing to detect whether my compounds activate cell death and survival pathway at the same time or not. Could anyone suggest me some signaling pathways or factors what I should consider in my assay?
PI3K/Akt Signalling pathway
http://www.ncbi.nlm.nih.gov/pubmed/15023437
May I ask which cytotoxicity assay you are using? and if you have noticed any difference between treated and control cells under the microscope?
and do you mean MDA-MB-231 cells instead of MDA BD-231 cells?
MDA-MB-231 cells belong to the triple negative breast cancer subtype and they are known to be aggressive, metastatic, and resistant to chemotherapy. 5 different mutations are reported to be present in this cell line, among which is the p53 missense mutation (Oliver 2002). Your question is very broad as an interplay between many signaling pathways can confer resistance to your compounds. I suggest you take a breast cancer cell line that is usually responsive to targeted therapy or chemotherapy such as MCF-7, and characterize your drugs on that cell line. If your compounds were shown to be effective on MCF-7 but not on MDA-MB-231, then you can start looking at differentially expressed genes between these two cell lines, and identifying those that confer sensitivity/resistance to your treatment by a series of knockdown and overexpression.
Best,
Patrick
I like a thorough response by Patrick. However, one should refrain from concentrating on the cancer cell line (i.e., MDA.MB.231) alone as a sole player for inducing chemoresistance. Perhaps, cancer centric view to chemoresistace could be one of the major factors that leads to failure of chemotherapy.
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