体外研究
(In Vitro) |
P-gp/BCRP-IN-1 (compound 19) (0-200 μM, 48 h) has a weak anti-proliferative activity against A549 cells, and shows low cytotoxicity to the K562 , K562/A02, MDCK-II, MDCK-II-BCRP cells[1].
P-gp/BCRP-IN-1 (48 h) exhibits the great reversal effect of resistance to both ADM (Adriamycin) and MX (Mitoxantrone) in K562/A02 cells and MDCK-II-BCRP cells, and increases the reversal activity of ADM (0-5 μM) and MX (0-20 μM) in a concentration-dependent manner[1].
P-gp/BCRP-IN-1 (0-5 μM, 4 h) increases drug accumulation and prevents efflux of P-gp and BCRP[1].
P-gp/BCRP-IN-1 (0-5 μM, 48 h) dose not affect the expression of P-gp as well as BCRP protein[1].
P-gp/BCRP-IN-1 (0-200 μM, 4 h) decreases the viability of Caco-2 cells, inhibits the intestinal P-gp-mediated efflux of PTX and increases its concentration in the intestinal cells, can enhance the absorption and bioavailability[1].
P-gp/BCRP-IN-1 prevents intracellular accumulation of anti-neoplastic drugs by impairing the function of P-gp and BCRP[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay
| Cell Line: |
A549 cells, chemo-sensitive cell lines (K562, MDCK-II), chemo-resistant cell lines (K562/A02, MDCK-II-BCRP)[1] |
| Concentration: |
200, 100, 50, 25, 12.5, 6.25, 3.125, 1.56 and 0 μM |
| Incubation Time: |
24, 48 h |
| Result: |
Had a weak anti-proliferative activity against A549 cells, with an IC50 of 46.28 μM, and showed low cytotoxicity to the K562 , K562/A02, MDCK-II, MDCK-II-BCRP cells, with IC50 values of 72.81, 43.29, 87.69, 81.22 μM, respectively. |
Cell Viability Assay
| Cell Line: |
K562/A02 cells and MDCK-II-BCRP cells[1] |
| Concentration: |
5 μM |
| Incubation Time: |
48 h |
| Result: |
Increased the reversal activity of ADM (0-5 μM) and MX (0-20 μM) in a concentration-dependent manner, exhibited the great reversal effect of resistance to both ADM and MX in K562/A02 cells and MDCK-II-BCRP cells, with IC50 values (at 5 μM) of 2.41 and 18.43 μM, RF (reversal fold, at 5 μM) of 40.51 and 37.40, and EC50of 65.31 and 98.22 nM, respectively. |
Western Blot Analysis
| Cell Line: |
K562/A02 cells and MDCK-II-BCRP cells, K562 and MDCK-II cells.[1] |
| Concentration: |
0, 0.5, 1, 5 μM |
| Incubation Time: |
48 h |
| Result: |
Did not affect the expression of P-gp as well as BCRP protein, exerted resistance reversal without affecting the expression of P-gp as well as BCRP protein, but probably by inhibiting the efflux function of P-gp and BCRP. |
Cell Viability Assay
| Cell Line: |
Caco-2 cells[1] |
| Concentration: |
1.25, 5, 10, 20, 30, 50, 100, 200 μM |
| Incubation Time: |
4 h |
| Result: |
Decreased the viability of Caco-2 cells to less than 20% at concentrations of 30 and 50 μM respectively, significantly decreased the Papp (apparent permeability coefficient) value, inhibited the intestinal P-gp-mediated efflux of PTX and increased its concentration in the intestinal cells, which could eventually enhance the absorption and bioavailability of the orally administered drug. |
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