Synthesis and reversal effect of a novel N-substituted phthalimide-sugar on doxorubicin resistant of human breast cancer cells

Abstract

Abstract:

Thalidomide (α-N-phthalimido-glutarimide, TLD) is a kind of anti-angiogenic and anti-inflammatory drug, and showed effects in the treatment of several disease entities. In this study, the biological effects of a novel N-sugar substituted phthalimide (STA-35) on the regulation of multidrug resistance (MDR) to doxorubicin (ADR) were investigated. The proliferation of cancer cells was detected by a SRB assay. The activity of P-glycoprotein (P-gp) was determined by a Flow cytometry. The expression of P-gp was measured by western blotting. The results showed that STA-35 inhibited the proliferation of human breast cancer cell line MCF-7 and its ADR resistant cell line MCF-7/ADR, and the relative resistance was only 1.19. Meanwhile, STA-35 could sensitize the cytotoxicity of ADR in MCF-7/ADR cells. In addition, we found that STA-35 reduced the activity of P-gp by suppressing the P-gp expression, which was indicated by the increase in the accumulation of rhodamine 123 in MCF-7/ADR cells. These results suggested a promising application of STA-35 as the MDR reversing agent. The underlying mechanism of the effects might be attributed to the inhibition of P-gp.

Key words: Multidrug resistance, Multidrug resistance, Thalidomide, Thalidomide, Phthalimide, Phthalimide, P-glycoprotein, P-glycoprotein

Supporting:

Wen-Yuan Yi, Min Li^*, Ya-Ping Yang, Zhuo-Yuan Lu, Bo Xu, Dong Han, Zhong-Jun Li^*^*, Jing-Rong Cui

. Synthesis and reversal effect of a novel N-substituted phthalimide-sugar on doxorubicin resistant of human breast cancer cells
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