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 maintenance treatment.We analyzed resistance and survival signals in U87 MG cells using popularfilm.blog 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, apoptosis, and autophagy signaling to ensure survival.In these groups TMZ and etoposide efficiency dramatically reduced.Our result suggests that combined high-dose treatments of classical antineoplastic agents to sensitize tumors may trigger multi-drug resistance and inhibit maintenance treatment.When deciding on antineoplastic combination therapy for persistent/resistant glioblastoma, we recommend analyzing the long-term hormetic and opi the color that keeps on giving chronic effects on cross-resistance and multi-drug resistance in primary cell cultures from patients.