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1. Mol Med. 2012 Apr 25. doi: 10.2119/molmed.2011.00444. [Epub ahead of print]

Axitinib targeted cancer stem-like cells to enhance efficacy of chemotherapeutic
drug via inhibiting the drug transport function of ABCG2.

Wang F, Mi YJ, Chen XG, Wu XP, Liu Z, Chen SP, Liang YJ, Cheng C, Fu LW.

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen
University, Guangzhou 510060, China.

Stem-like cells have been isolated by their ability to efflux Hoechst 33342 dye
and are referred to as the "side population" (SP). Here, we evaluated the effect
of axitinib on targeting cancer stem-like cells and enhancing the efficacy of
chemotherapeutical agents. We found axitinib could enhance the cytotoxicity of
topotecan and mitoxantrone in SP cells sorted from human lung cancer A549 cells
and increase cell apoptosis induced by chemotherapeutical agents. Moreover,
axitinib particularly inhibited the function of ABCG2 and reversed ABCG2-mediated
multidrug resistance (MDR) in vitro. However, no significant reversal effect was
observed in ABCB1-, ABCC1- and LRP-mediated MDR. Furthermore, axitinib neither
altered the expression of ABCG2 at mRNA or protein levels, nor blocked
phosphorylation of AKT and ERK1/2 in both sensitive and MDR cancer cells. In nude
mice bearing ABCG2-overexpresing S1-M1-80 xenografts, axitinib significantly
enhanced the antitumor activity of topotecan without causing additional toxicity.
Taken together, these data suggest that axitinib particularly targets to cancer
stem-like cells and reverses ABCG2-mediated drug resistance by inhibiting the
transporter activity of ABCG2.

PMID: 22549112 [PubMed - as supplied by publisher]