Combined treatment with apatinib and docetaxel in A549 xenograft mice and its cellular pharmacokinetic basis

Acta Pharmacologica Sinica
Siqi FengFang Zhou

Abstract

Apatinib, a small-molecule inhibitor of VEGFR-2, has attracted much attention due to its encouraging anticancer activity in third-line clinical treatment for many malignancies, including non-small cell lung cancer (NSCLC). Its usage in second-line therapy with chemotherapeutic drugs is still under exploration. In this study we investigated the antitumor effect of apatinib combined with docetaxel against NSCLC and its cellular pharmacokinetic basis. A549 xenograft nude mice were treated with apatinib (100 mg/kg every day for 20 days) combined with docetaxel (8 mg/kg, ip, every four days for 5 times). Apatinib significantly enhanced the antitumor effect of docetaxel and alleviated docetaxel-induced liver damage as well as decreased serum transaminases (ALT and AST). LC-MS/MS analysis revealed that apatinib treatment significantly increased the docetaxel concentration in tumors (up to 1.77 times) without enhancing the docetaxel concentration in the serum, heart, liver, lung and kidney. Furthermore, apatinib decreased docetaxel-induced upregulation of P-glycoprotein in tumors. The effects of apatinib on the uptake, efflux and subcellular distribution of docetaxel were investigated in A549 and A549/DTX (docetaxel-resistant) cells in...Continue Reading

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Citations

Aug 13, 2021·Pharmaceutical Research·K SouleleP Macheras
Aug 28, 2021·International Journal of Molecular Sciences·Mi-So JeongSeong-Gyu Ko

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Methods Mentioned

BETA
xenograft
xenografts
protein assay
reverse transcription PCR
electrophoresis

Software Mentioned

Image Lab
SPSS

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