Participation of mTOR in the regulation of multidrug resistance of tumor cells

• Published in: Biochemistry (Moscow). Supplement series A, Membrane and cell biology Vol. 3; no. 2; pp. 184 - 189
• Main Authors: Scherbakova, E. A., Rybalkina, E. Yu, Stromskaya, T. P., Stavrovskaya, A. A.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01-06-2009; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Cell Biology; Drug resistance; Glycoproteins; Life Sciences; Signal transduction; Tumors; mTOR protein; multidrug resistance; ABC transporters; tumor cells; rapamycin
• ISSN: 1990-7478; 1990-7494
• DOI: 10.1134/S1990747809020111

Molecular mechanisms of the influence of PI3K/Akt/PTEN/mTOR-signaling pathway on survival of tumor cells treated with cytotoxic drugs was studied using rapamycin (Rapa), mTOR specific inhibitor, and 9 human tumor cell lines of different origin and with different Akt kinase activity. Three of these cell lines were selected for drug resistance due to P-glycoprotein (Pgp or ABCB1) overexpression. Rapa inhibited phosphorylation of mTOR downstream effectors. Rapa sensitivity of the cells was Akt-dependent but did not correlate with ABCB1 overexpression. Suppression of mTOR function increased drug resistance in 8 out of 9 cell lines studied. The influence of Rapa on the ABC-transporter gene expression was examined. It was shown that in half of the cell lines studied Rapa exerted differential effects on the amount of ABC-transporter proteins: in some cases the protein amount decreased and in others, increased. The amount of mRNA remained unchanged. These data suggest that mTOR can regulate ABC transporters at the level of translation.