5 ul of ice cold nuclear extraction buffer and incubated on ice for 40 min with

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 5 ul of ice cold nuclear extraction buffer and incubated on ice for 40 min with Empty 5 ul of ice cold nuclear extraction buffer and incubated on ice for 40 min with

Post  jy9202 on Mon Feb 10, 2014 8:48 am

On the other hand, the PI3K Akt signals have been reported to regulate ARN-509 ic50 activity and trafficking of some transporters and or receptors, such as transferrin re ceptor, low density lipoprotein receptor, the amino acid transporter 4F2, integrin, and Glut1 through regulating endocytosis and recycling, There fore, the PI3K Akt signaling pathway might be involved in mechanisms of BCRP trafficking to the cell surface and maintenance of the pluripotency of stem cells. Another explanation was that some of the BCRP protein might be internalized, but expression levels of overexpessed BCRP in cancer cells are too high to discern internalized BCRP and most of BCRP would be left uninternalized. But, it was supposed that this hypothesis could not successfully explain the data that LY294002 clearly and remarkably sensitized MCF 7 BCRP cells to BCRP substrate drugs.

Accordingly, interaction of LY294002 with the drug binding sites of BCRP was thought to explain the reversal effects. Since BCRP overexpression did not result in acquisi tion of comparable degrees of LY294002 resistance with those of anticancer drugs, LY294002 would not be a transport substrate of BCRP but it would competitively interact AUY922 価格 with the drug binding site. Inhibitory effects of LY294002 on MRP1 and P gp LY294002 has been reported to competitively inhibit MRP1 mediated doxorubicin transport, Besides, MRP1 expression has been found to be regulated by the PI3K Akt pathway.

Treatment of myelogenous leukemia cells with wortmannin Alvocidib CDK 阻害剤 resulted in lower levels of phos phorylated Akt, downregulated MRP1 expression, and decreased rho123 extrusion in dye efflux assay, In another report, modulation of PI3K activity with the use of constitutively active and dominant negative inhibitors was found to affect the ability of prostate cancer cells to respond to chemotoxic treatments, MRP1 expres sion was upregulated as a consequence of PI3K activa tion in prostate cancer cells. Thus, LY294002 can also exert inhibitory effects on MRP1 function via dual mechanisms, i. e., competitive block of substrate trans port and modulation of expression. LY294002 has also been observed to antagonize trans port activity of P gp without influencing its expression and antagonize P gp mediated multidrug resistance, Authors of this report discussed that suppression of the apoptotic pathway and regulation mechanism of the transport activity controlled by the PI3K Akt kinase pathway might be additive to P gp mediated drug PI3K Akt pathway.

Taken together, LY294002 can inhibit all P gp, MRP1 and BCRP. Flavonoid as seeds of cancer chemotherapeutic drugs LY294002 was designed as a synthetic PI3K inhibitor based on quercetin, a naturally occurring flavonoid. Quercetin and other flavonoids had been found to re verse BCRP mediated drug resistance to variable degrees in the previous study, In fact, the chemical structure of LY294002 is very similar to those of quercetin and the strongest flavonoid that reverses BCRP mediated drug resistance, acacetin. But the chemical structures of wort mannin and PI 103 are quite different, Flavo noids are polyphenolic compounds which are abundant in fruits, vegetables, and plant derived beverages such as tea, green tea and wine.


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