Atinib improves the sensitivity of ABCG2 substrates not only in cells overexpressing wild-type, but also variants R482G / T ABCG2. Brivanib alaninate FGFR inhibitor Mechanically Like in other MDR inhibitors, lapatinib may be able to ABCB1 or ABCG2 resistance-mediated by the inhibition of efflux to reverse. accordance with this hypothesis, we found that incubation of MDR cells in combination with Herk has entered mmlichen chemotherapy and lapatinib Born an intracellular Re h accumulation of the drug Ago ABCB1 and ABCG2 in-expressing cells, the cells were incubated with drugs alone. A Hnliches result was obtained when the accumulation of rhodamine 123 examined in cells that ABCB1. In addition, inhibited the transport of E217G and methotrexate of lapatinib in a konzentrationsabh Ngigen way in membrane vesicles overexpressing wild-type ABCG2.
However, encourage the majority of substrates that interact with the ABC drug transporters ATP Dai et al. Page 11 Cancer Res Author manuscript, increases available in PMC 2009 1 October. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author proposed NIH manuscript hydrolysis and the fact that lapatinib stimulated TG100-115 PI3K inhibitor the ATPase activity of both ABCB1 and ABCG2 it Similar to other known substrates of this carrier Behave ger. These data led us to speculate that lapatinib interacts directly with Tr Like. Tats Chlich this was the best diagnosis Firmed that lapatinib significantly inhibited the binding of IAAP connection that the substrate-binding site of ABCB1 and ABCG2 drug photo labels.
Lapatinib but had no significant effect on the expression of ABCB1 in MCF 7/adr 80th ABCG2 in S1 and M1 cells These results suggest that lapatinib ABCB1 and ABCG2-mediated MDR inhibition of the function to which the expression of these two opposite pump reverses. The expression of EGFR and HER2 not substantially change, The toxicity t S1 of lapatinib in MCF 7/adr, S1 80 M1 cells or parental cells and MCF-7. Further studies in vitro on cell lines containing the wild type and mutant EGFR are carried out, k Can be useful in determining whether there is a difference in efficacy between tumors EGFR-expressing wild type or mutant. The observed toxicity t of lapatinib in relatively high concentrations can not be produced by a process of phosphorylation of EGFR. But in this study, we have not the m Resembled mechanisms of toxicity t of lapatinib studied in our cell lines.
In summary, lapatinib is cellular Inhibit ABCB1 and ABCG2 Ren functions at clinically relevant concentrations. The inhibition of efflux as a result of direct interaction of lapatinib with ABCB1 or ABCG2 may result in increased Hten clinical response when using Herk Mmlichen combined chemotherapy. Our analysis of the inversion effect of lapatinib in tumor xenograft model showed that the combination of lapatinib with other anticancer drugs may be important to overcome the clinical resistance to chemotherapy in cancer. See erg Complementary materials to the Web version on PubMed Central erg Complementary materials. Acknowledgments We thank Dr. Susan E. Bates for S1 and S1-80 M1 cells, and the FTC, Dr. Somnath Pal using statistical analysis, Dr. Jian Zhang for technical support, JE, Shen Tong and Chen Yangmin for editorial support of the manuscript. This work was supported by funds from the China National Natural Science Foundation No.30672407 and 863 Project Foundation No.2006AA09Z41