AIM： To investigate the reversal effect of LY980503, a benflumetol derivative, on multidrug resistance in vincristine （VCR） -resistant human gastric carcinoma cell line SGC7901/VCR. METHODS： Cells of a human gastr...AIM： To investigate the reversal effect of LY980503, a benflumetol derivative, on multidrug resistance in vincristine （VCR） -resistant human gastric carcinoma cell line SGC7901/VCR. METHODS： Cells of a human gastric cancer cell line, SGC7901, and its VCR-resistant variant, SGC7901/VCR, were cultivated with LY980503 and/or doxorubicin （DOX）. The cytotoxicity of drugs in vitro was assayed by M-IF method. Based on the flow cytometric technology, the uptake of DOX was detected in these cells by measuring DOX -associated mean fluorescence intensity （MFI）. RESULTS： SGC7901/VCR cells were 23.5 times more resistant to DOX in comparison with 5GC7901 cells. LY980503 at the concentrations of 2.0 μmol/L -10 μmol/ L had no obvious cytotoxicity to SGC7901 and SGC7901/ VCR cells. After simultaneous treatment with LY980503 at the concentrations of 2.0, 4.0 and 10 μmol/L, the ICso of DOX to SGC7901/VCR cells decreased from 1.6 ± 0.12 μmol/L to 0.55 ± 0.024, 0.25 ± 0.032 and 0.11 ± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 2.9-fold （P 〈 0. 05）, 6.4-fold （P 〈 0. 01） and 14.5-fold （P 〈 0. 01）, respectively. In the uptake study of DOX, simultaneous incubation of SGC7901/VCR cells with LY980503 significantly increased the DOX -associated MFI in SGC7901/VCR cells. No such results were found in parental SGC7901 cells.CONCLUSION： LY980503 at non-cytotoxic concentrations can effectively circumvent resistance of SGC7901/VCR cells to DOX by increasing intracellular DOX accumulation.展开更多
基金Supported by National Natural Science Foundation of China, No. 39800181
文摘AIM： To investigate the reversal effect of LY980503, a benflumetol derivative, on multidrug resistance in vincristine （VCR） -resistant human gastric carcinoma cell line SGC7901/VCR. METHODS： Cells of a human gastric cancer cell line, SGC7901, and its VCR-resistant variant, SGC7901/VCR, were cultivated with LY980503 and/or doxorubicin （DOX）. The cytotoxicity of drugs in vitro was assayed by M-IF method. Based on the flow cytometric technology, the uptake of DOX was detected in these cells by measuring DOX -associated mean fluorescence intensity （MFI）. RESULTS： SGC7901/VCR cells were 23.5 times more resistant to DOX in comparison with 5GC7901 cells. LY980503 at the concentrations of 2.0 μmol/L -10 μmol/ L had no obvious cytotoxicity to SGC7901 and SGC7901/ VCR cells. After simultaneous treatment with LY980503 at the concentrations of 2.0, 4.0 and 10 μmol/L, the ICso of DOX to SGC7901/VCR cells decreased from 1.6 ± 0.12 μmol/L to 0.55 ± 0.024, 0.25 ± 0.032 and 0.11 ± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 2.9-fold （P 〈 0. 05）, 6.4-fold （P 〈 0. 01） and 14.5-fold （P 〈 0. 01）, respectively. In the uptake study of DOX, simultaneous incubation of SGC7901/VCR cells with LY980503 significantly increased the DOX -associated MFI in SGC7901/VCR cells. No such results were found in parental SGC7901 cells.CONCLUSION： LY980503 at non-cytotoxic concentrations can effectively circumvent resistance of SGC7901/VCR cells to DOX by increasing intracellular DOX accumulation.
