Abstract 349P
Background
It is assumed that aggressiveness and therapy resistance of glioblastoma multiforme (GBM) is determined by its high heterogeneity and presence of cancer stem cells (CSC). The primary glioblastoma cell lines (pGBM lines) could better than the cultured cell lines reflect the tumor heterogeneity and, thus, provide the additional opportunities for personalized medicine. In our study, we compared the response of the pGBM lines and cell glioblastoma lines to chemotherapy drugs with the CSC content in cell cultures.
Methods
Four pGBM lines obtained from patients and standart glioblastoma line U251 were used. The amount of CSCs in cell culture was evaluated with flow cytometry by expression of CD133/CD44 and CD90/CD95. Further, the cultures were characterized by immunostaining with Nestin and Oct4.Chemotherapeutic agents included both drugs, commonly used in clinical practice for glioblastoma treatment and drugs used for therapy of other types of cancer. Cytotoxicity was tested via MTT assay. Proliferation rate was measured through cell counting within 3 following days.
Results
The correlations between CD133/ CD44 and CD90/CD95 expression, proliferation rate, and drug resistance of cell cultures were evaluated. The U251 cell line demonstrated significantly increased sensitivity towards cytostatic agents such as gemcitabinum, cisplatin, irinotecan, doxorubicin as compared to pGBM-lines, although its proliferation rate was not the highest. For all studied GBM-lines, the amount of CD90+/CD95+ cells negatively correlated with rozustin sensitivity. The Gbl24n line was the only cell culture with CD133+ cells (about 10%) and it was 20-25% less sensitive to lomustine. Carfilzomib sensitivity positively correlates with the amount of CD133-/CD44- cells, whereas irinotecan sensitivity has a negative correlation with this parameter.
Conclusions
In total, the pGBM lines are less sensitive to anti-cancer drugs, than the U251 cell line. That might result from heterogeneity of primary culture and the presence of CSC in primary tumor cultures. For several drugs (lomustine), the correlation between the amount of CSC in cell culture and drug sensitivity was found.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.