Year-end Sale % OFF 
Abstract
Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured GBM cells with human astrocytes in three-dimensional (3D) poly(ethylene glycol) dimethyl acrylate (PEGDA) microwells to mimic the tumor microenvironment. We treated 3D co- and mono-cultured cells with Temozolomide (TMZ) and the nuclear factor-κB (NF-κB) inhibitor Bay 11-7082 and investigated the combined effect of the drugs. We assessed the expressions of glial fibrillary acidic protein (GFAP) and vimentin that play a role in the tumor malignancy and activation of the astrocytes as well as Notch-1 and survivin that play a role in GBM malignancy after the drug treatment to understand how astrocytes induced GBM drug response. Our results showed that in the co-culture, astrocytes increased GBM survival and resistance after combined drug treatment compared to mono-cultures. These data restated the importance of 3D cell culture to mimic the tumor microenvironment for drug screening.
Highlights
Glioblastoma multiforme (GBM), a grade IV tumor based on the WHO classification, is the most common malignant type of astrocytic tumors [1]
Our results indicated that after the combined drug treatment, gene expressions of glial fibrillary acidic protein (GFAP), vimentin, Notch-1, and survivin were significantly downregulated by 0.24, 1, 1.5, and 0.23-fold, respectively, in the co-culture, 0.06, 0.14, 0.13, and 0.07-fold, respectively, in the LN229 mono-culture (p < 0.01), and 0.13, 0.6, 0.14, and 0.15 in the astrocyte mono-culture (p < 0.05) (Figure 4a–d)
TMZ resistance is responsible for GBM tumor recurrences in most patients [33]
Summary
Glioblastoma multiforme (GBM), a grade IV tumor based on the WHO classification, is the most common malignant type of astrocytic tumors [1]. The underlying molecular mechanism of TMZ resistance is more complex than its dependence on MGMT expression [8]. Another mechanism that is associated with TMZ resistance in GBM is the excessive activation of Nuclear Factor-κB (NF-κB) [9]. It was shown that NF-κB inhibitor Bay 11-7082 suppressed MGMT and promoted TMZ-induced cytotoxicity and apoptosis in U251 GBM cells [8]. This suggests that the combination of TMZ and Bay 11-7082 drugs have a combinatorial effect of inhibiting GBM growth [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
