Reversal of multidrug resistance of cancer through inhibition of P-glycoprotein by 5-bromotetrandrine

Cancer Chemotherapy and Pharmacology
Jing JinGengtao Liu

Abstract

The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro and in vivo. Drug sensitivity was determined using the MTT assay. The in vivo effect of Tet was investigated using nude mice grafted with sensitive and resistant KB human epidermoid cancer cells. Doxorubicin (Dox) accumulation was analyzed by fluorospectrophotometry and the protein and mRNA levels of P-glycoprotein (P-gp) were determined by immunocytochemistry and RT-PCR, respectively. BrTet at 0.25, 0.5 and 1 micro M reversed Dox resistance in MDR human breast cancer MCF-7/Dox cells dose-dependently and its potency was greater than that of Tet at the same concentrations. BrTet reversed vincristine (VCR), Dox and paclitaxel resistance in MDR human oral epidermoid carcinoma KBv200 cells as well as innate VCR and Dox resistance in human hepatocellular carcinoma Bel(7402) cells. However, BrTet showed no effect on the IC(50) values of the above-mentioned anticancer drugs in sensitive MCF-7 and KB cells. No reversal effect of BrTet on the cytotoxicity of 5-fluorouracil and cisplatin, non-P-gp substrates, was observed. In nude mice bearing KBv200 xenografts on the left flank and KB xenografts...Continue Reading

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Citations

Sep 6, 2011·Oncogene·L GalluzziG Kroemer
Nov 13, 2009·Photochemistry and Photobiology·Arménio SerraMaria Filomena Botelho
May 8, 2009·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Hong ZhangWanqing Liao
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