ANTINEOPLASTIC MULTI-DRUG CHEMOTHERAPY TO SENSITIZE TUMORS TRIGGERS MULTI-DRUG RESISTANCE AND INHIBITS EFFICIENCY OF MAINTENANCE TREATMENT IN GLIOBLASTOMA CELLS
Küçük Resim Yok
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Excli Journal Managing Office
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Combinations of the well-known antineoplastic agents 5-fluorouracil (5-Fu), cisplatin, and paclitaxel are employed to increase radiotherapy/immunotherapy efficacy against persistent and resistant tumors. However, data remains needed on the hormetic, chronic, and long-term side effects of these aggressive combination chemotherapies. Here we investigated cellular and molecular responses associated with these combined agents, and their potential to induce multi-drug resistance against the temozolomide (TMZ) and etoposide (EP) used in glioblastoma mainte-nance treatment. We analyzed resistance and survival signals in U87 MG cells using molecular probes, fluorescent staining, qRT-PCR, and immunoblot. Repeated treatment with combined 5-Fu, cisplatin, and paclitaxel induced cross-resistance against TMZ and EP. Resistant cells exhibited elevated gene/protein expression of MRP1/ABCC1, ABCC2, BRCP/ABCG2, and GST. Moreover, they managed oxidative stress, cell cycle, apopto-sis, and autophagy signaling to ensure survival. In these groups TMZ and etoposide efficiency dramatically re-duced. Our result suggests that combined high-dose treatments of classical antineoplastic agents to sensitize tu-mors may trigger multi-drug resistance and inhibit maintenance treatment. When deciding on antineoplastic com-bination therapy for persistent/resistant glioblastoma, we recommend analyzing the long-term hormetic and chronic effects on cross-resistance and multi-drug resistance in primary cell cultures from patients.
Açıklama
Anahtar Kelimeler
Glioblastoma, Multi-Drug Resistance, Apoptosis, Autophagy, Angiogenesis, U87 MG, Molecular-Mechanisms, Drug-Resistance, Cancer, Hypoxia, Paclitaxel, Autophagy, Temozolomide, Survival
Kaynak
Excli Journal
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
22
