Objective： To investigate the reversal effect of CQ11, a chloroquine derivative, on multidrug resistance （MDR） in doxorubicin （DOX）-resistant human breast carcinoma cell line MCF/DOX. Methods： Cells of a human b...Objective： To investigate the reversal effect of CQ11, a chloroquine derivative, on multidrug resistance （MDR） in doxorubicin （DOX）-resistant human breast carcinoma cell line MCF/DOX. Methods： Cells of a human breast cancer cell line, MCF, and its DOX-resistant variant, MCF/DOX, were cultivated with DOX and/or CQ11. The cytotoxicity of drugs in vitro was assayed by MTT method. The accumulation of DOX in these cells was detected by fluorescence spectrophotometer. Results： MCF/DOX cells were 119 times more resistant to DOX in comparison with M CF cells. After simultaneous treatment with CQ 11 at the concentrations of 1.0, 2.5 and 5.0 μmol/L, the IC50 of DOX for MCF/DOX cells decreased from 3.1 ±0.47 μmot/L to 0.58 ± 0.032, 0.19 ± 0.012 and 0.081 ± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 5.3-fold （P 〈 0.01）, 16- fold （P 〈 0.01） and 38-fold （P 〈 0.01）, respectively. In the accumulation assay of DOX, simultaneous incubation of MCF/DOX cells with CQ11 significantly increased the DOX accumulation in MCF/DOX cells. No such results were found in parental MCF cells. Conclusion： CQ11 had strong MDR reversal effect by enhancing intracellular DOX accumulation in MCF/DOX cells, indicating that CQ11 may be a promising MDR chemosensitivity.展开更多
基金the National Natural Science Foundation of China (No. 39800181)the Research Foundation of Jiaxing Science and Technology Bureau (No. 2007AY2033)the Research Foundation of Jiaxing College (No. 70107032)
文摘Objective： To investigate the reversal effect of CQ11, a chloroquine derivative, on multidrug resistance （MDR） in doxorubicin （DOX）-resistant human breast carcinoma cell line MCF/DOX. Methods： Cells of a human breast cancer cell line, MCF, and its DOX-resistant variant, MCF/DOX, were cultivated with DOX and/or CQ11. The cytotoxicity of drugs in vitro was assayed by MTT method. The accumulation of DOX in these cells was detected by fluorescence spectrophotometer. Results： MCF/DOX cells were 119 times more resistant to DOX in comparison with M CF cells. After simultaneous treatment with CQ 11 at the concentrations of 1.0, 2.5 and 5.0 μmol/L, the IC50 of DOX for MCF/DOX cells decreased from 3.1 ±0.47 μmot/L to 0.58 ± 0.032, 0.19 ± 0.012 and 0.081 ± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 5.3-fold （P 〈 0.01）, 16- fold （P 〈 0.01） and 38-fold （P 〈 0.01）, respectively. In the accumulation assay of DOX, simultaneous incubation of MCF/DOX cells with CQ11 significantly increased the DOX accumulation in MCF/DOX cells. No such results were found in parental MCF cells. Conclusion： CQ11 had strong MDR reversal effect by enhancing intracellular DOX accumulation in MCF/DOX cells, indicating that CQ11 may be a promising MDR chemosensitivity.
