Abstract
Purpose: Glioblastoma multiforme is the most frequent malignant brain tumor as well as one of the most lethal and untreatable human tumors with a very poor survival rate (up to 18 months). Thus, novel and effective strategies of treatment are still required since resistance and metastasis are major problems of anticancer chemotherapy. Interestingly, ABC transporters, which play a crucial role in the development of multidrug resistance, are modulated by phenothiazine derivatives, while cancer metastasis, migration, and invasion are regulated by cadherins, α-tubulin, and integrins. Methods: The impact on the motility of human glioblastoma U87-MG was performed by wound healing assay, cellular migration and invasion were performed by transwell assay, while ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins (α3, α5, and β1) content were determined by Western blot.Results: The present study explores the effect of perphenazine and prochlorperazine on ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins (α3, α5, and β1) amount as well as migration and invasion ability of human glioblastoma (U87-MG) cells suggesting that phenothiazine derivatives impair multidrug resistance proteins (ABCB1 and ABCG2), E-cadherin, α-tubulin, and integrins amount as well as impair migration and invasion of the U87-MG cell line. Conclusions: The study demonstrated that an increase of ABCG2 and E-cadherin as well as a decrease of α-tubulin, and integrins amount may explain the decrease of migration and invasion ability after phenothiazine derivatives treatment. Moreover, only prochlorperazine significantly reduces the rate of cell migration. Thus, the drug may be considered for the development of new and effective glioblastoma therapy.