Transfected LY315920 172732-68-2 SIU mitoxantrone in three cell lines ABCG2 ABCG2 482 R5, ABCG2 and ABCG2 482,482 G2 T7 cells were significantly h Ago than in the parental cell line HEK293/pcDNA3.1 cells. Lapatinib, an amount of 2.5 to 10 M, a significant reduction of the IC 50 value for mitoxantrone and reversed resistance to mitoxantrone in cells expressing wild type or mutant ABCG2. In addition, the effect of lapatinib was reverse 10M Similar to that of the specific ABCG2 inhibitor FTC at 2.5 M and h Quality here T as those of another EGFR inhibitor erlotinib TK to 10 n M. It “There was no significant difference in the IC50 values for mitoxantrone in the presence or absence of lapatinib HEK293/pcDNA3 cells. In addition, lapatinib does not materially impair changed IC50 values of cisplatin, which is not a substrate ABCG2 in all cell lines.
These results suggest that lapatinib specifically improved the sensitivity of ABCG2 PIK-90 PI3K inhibitor substrates in cells expressing wild-type or mutant R482G / T ABCG2. Dai et al, Cancer Res. page 7 Author manuscript, increases available in PMC 2009 October 1. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH lapatinib increased ht the trailer show ufung of chemotherapeutic drugs in MDR cells overexpressing ABCB1 and ABCG2 The above results indicate that lapatinib, the sensitivity of MDR cells to certain chemotherapeutic agents hen to increased. The mechanism of this occurs is unknown. Therefore, we examined the effects on the accumulation of doxorubicin in MCF 7/adr express ABCB1 and parental MCF-7 cells. Fig.
1A, the effect of lapatinib shows on accumulation of doxorubicin in the MCF and MCF 7 / 7-adr cells. The accumulation of doxorubicin was significantly more hours 7/adr forth in sensitive cells MCF-7 cells than in MDR MCF. However, the level of accumulation of doxorubicin in drug development sensitive MCF-7 cells not by concentrations of lapatinib 0.625, 1.25 or 2.5 m of lapatinib affected. In the absence of lapatinib was lower doxorubicin accumulation in MCF 7/adr lapatinib and returned to the level of accumulation of doxorubicin than the parental cells in a dose- ngigen way. The intracellular re accumulation of doxorubicin was 1.5, 2.9, 3.6 hr time 7/adr forth in MCF in the presence of 0.625, 1.25 or 2.5 M lapatinib, respectively. As shown in Fig. 1B, in all cells overexpress ABCG2, lapatinib to 1 M and 2.
5 M produced a konzentrationsabh Independent erh increase the intracellular Ren accumulation of mitoxantrone, and the effects of lapatinib to 2.5 M were similar to the FTC and 2.5 M However, lapatinib did not significantly show the intracellular re accumulation of mitoxantrone in HEK293/pcDNA3.1 cells. These results indicate that lapatinib is able to addicted write was the intracellular re accumulation of chemotherapeutic drugs into cells or ABCG2 ABCB1. Lapatinib inhibits the transport of methotrexate by ABCG2 E217G and wild-type best for another term, the effect of lapatinib on the Transportaktivit t of ABCG2, we used membrane vesicles from cells and ABCG2 HEK293/pcDNA3 R5 482 to perform inhibition experiments. We have these two cell lines , which isolates the rate of ATP absorption of methotrexate, an antifolate anticancer drug and a substrate of ABCG2 in membranes from cells HEK293/pcDNA3.1 significantly from membrane vesicles ABCG2 cells R5 482 but was not