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沙利度胺(α-N-phthalimido-glutarimide,TLD)是一种具有抗血管生成和抗炎作用的药物,对多种实体瘤有效。本文研究了N-精基取代的沙利度胺新衍生物(STA-35)对阿霉素(doxorubicin,ADR)引起的多药耐药(multidurg resistance,MDR)的调节作用。采用SRB法检测化合物对癌细胞的增殖抑制作用,应用流式细胞术测定P-糖蛋白(P-glycoprotein,P-gp)的功能,以免疫印迹方法考察P-gp的蛋白表达。实验结果表明,STA-35能够抑制人乳腺痛细胞MCF-7及其ADR耐药细胞MCF-7/ADR生长,耐药指数仅为1.19;并能增强MCF-7/ADR细胞对ADR的敏感性。此外,STA-35可以增加MCF-7/ADR细胞内罗丹明123(rhodamine 123,RH123)的聚积,减弱P-gp的功能,抑制P-gp的蛋白表达。该化合物具有多药耐药逆转作用,其分子机制可能与抑制P-gp的功能和蛋白表达相关。
Thalidomide (α-N-phthalimido-glutarimide, TLD) is an anti-angiogenic and anti-inflammatory drug that is effective for many solid tumors. In this paper, we investigated the modulation of multidrug resistance (MDR) induced by adriamycin (doxorubicin, ADR) by a new derivative of thalidomide (STA-35). The inhibitory effect of the compound on the proliferation of cancer cells was detected by SRB method. The function of P-glycoprotein (P-gp) was determined by flow cytometry. The protein expression of P-gp was examined by immunoblotting. The results showed that STA-35 could inhibit the growth of human mammary gland MCF-7 and its ADR resistant cell MCF-7 / ADR, the resistance index was only 1.19; and it also enhanced the sensitivity of MCF-7 / ADR cells to ADR . In addition, STA-35 can increase the accumulation of rhodamine 123 (RH123) in MCF-7 / ADR cells, weaken the function of P-gp and inhibit the expression of P-gp protein. The compound has multidrug resistance reversal effect, and its molecular mechanism may be related to the inhibition of P-gp function and protein expression.