AMPA Receptor in clinical trials is the BPR1K653 of the MDR1 gene expression in cancer cells

Cancer cells independent Ngig of their origin and tissue p53 status. AMPA Receptor in clinical trials BPR1K653 is as in inhibiting the growth of multidrug resistance protein expressing cancer cells, it generally shown that the expression of MDR1 in drug-induced resistance to various chemotherapeutic agents. To determine whether the power is the BPR1K653 of the MDR1 gene expression in cancer cells, three multidrug-resistant MDR1-expressing cell lines KBVIN10, KB NTU0.017 and S15 removed, were treated with BPR1K653. As was shown VIN10 S15 in Table 3, the IC50 value of KB and KB BPR1K653 Similar to the parental cells MDR1 negative KB. The IC50 of BPR1K653 to VIN10 KB, KB and KB S15 were 14 nm to 11 nm and 12. In addition, the IC50 value of the MDR1-expressing cells was also BPR1K653 NTU0.017 Similar to MDR1 negative parenting NTUB1 cells.
Previous studies have shown that inhibitors of Aurora kinase, VX680 and PHA739358, substrates of MDR1. Consistently showed all of our MDR1 expressing tumor cell lines androgen receptor antagonists patent cross-resistant to PHA739358 and VX680. In addition, correlates the H Height of expression of the MDR1 gene with the value of the resistor to determine whether BPR1K653 VX680/PHA 739,358 f to apoptosis induction Hig MDR1 in both positive and negative cancer cells, KB and KB cells is VIN10 were BPR1K653 treated and apoptotic properties were annexin V, real-time imaging caspase 3/7 activity t and TUNEL tests analyzed. Here, both the cytoplasmic volume and Kerngr E in the treated and KBVIN10 BPR1K653 KB cells obtained Ht, indicating that endoreplication normal BPR1K653 induced cell.
The translocation of phosphatidylserine to the molecule of the cell membrane innerleaflet U Ere membrane shows the incidence of early apoptosis. The test results showed that annexin JNJ-26481585 V BPR1K653 translocation of the molecule both KB and KB cells VIN10 phosphatidylserine, is a guide to the green fluorescent label. BPR1K653 also induces the activity t of caspase 3/7 and DNA fragmentation in both KB and KB VIN10 cells under the same processing conditions. In contrast, only induced VX680 translocation of the molecule phosphatidylserine, caspase 3/7 activity T and DNA fragmentation in KB cells and not in the MDR1-expressing cells KB VIN10. In addition, cleavage of PARP been found that the MDR1 expressing KB cells with either VIN10 BPR1K653 or VX680/verapamil treated not only with VX680, as demonstrated by Western blot analysis.
BPR1K653 induced apoptosis in cells HONE 1 as shown by the induction of caspae 3/7 activity t in vitro. BPR1K653 suppresses the growth of two human MDR1 xenografts negative and positive in vivo Although showed the above results that the exposure BPR1K653 strong anti-cancer effects in vitro, experiments were performed to determine if is BPR1K653 also able to inhibit the activity t of Aurora kinases and the growth of two tumors, MDR1 negative / positive in vivo. KB cells were grown as sc tumors in mice Nacktm. If it is well established xenografts KB Concrete tumor size E, 75 mm 3 were, were the Mice Feeder Controlled llig The vehicle and treatment groups of five animals. The treated M Mice again U or 15 mg / kg BPR1K653 or 30 mg / kg ip for 5 days VX680 weeks fo