Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Non-responsive subpopulation of tumor cells, and acquired resistance in initially responsive cells are major challenges for cancer therapy with molecularly-targeted drugs. While point mutations are considered the major contributing factor to acquired resistance, in this study we explored the role of heterogeneity and plasticity of selected human breast cancer cell lines (MDA-MB-231, MDA-MB-468, and AU565) in their initial and adjusted response, respectively, to ruxolitinib, everolimus, and erlotinib. After determination of lethal concentration for 50% cell death (LC50), cells were exposed to selected drugs using three different approaches: single exposure to 4 × LC50 and collection of surviving cells, multiple exposures to 1.5 × LC50 and monitoring the surviving population, and exposure to gradually increasing concentrations of selected drugs (range of concentrations equivalent to 10% of LC50 to 1.5 × LC50). Surviving cells were studied for adjustments in expression level of selected proteins using quantitative PCR and Western Blot. Our data indicated overexpression of a variety of proteins in resistant populations, which included cell membrane receptors EGFR and HER2, anti-apoptotic proteins Bcl-2 and BIRC8, and other proteins involved in cell signaling (e.g., Akt1, MAPK7, and RPS6KA5). Silencing the identified alternative proteins via siRNA resulted in significant drop in the LC50 of the selected molecularly-targeted drugs cells resistant to ruxolitinib (via targeting Akt), everolimus (via targeting EGFR, MAPK7, RPS6KA5, and HER2), and erlotinib (via silencing Bcl2 and BIRC8). Our data indicates that targeting well-selected alternative proteins could potentially sensitize the resistant cells to the effect of the molecularly-targeted treatment.
Pubmed ID: 31681603
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets ErbB2/Her2
View all literature mentionsThis polyclonal targets Goat Mouse IgG HRP Affinity Purified PAb
View all literature mentionsThis monoclonal targets Human Jak3, aa 46-209
View all literature mentionsThis monoclonal targets Human EGF R / ErbB1
View all literature mentionsThis monoclonal targets Human MSK1
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Akt1
View all literature mentionsThis monoclonal targets Human/Mouse/Rat Bcl-2 MAb (Clone 625509)
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis monoclonal targets ERK5
View all literature mentionsCell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AU565 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions