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[目的]探讨丹参酚酸B(Sal-B)对人大肠癌多药耐药细胞HCT-8/VCR耐药的逆转作用,并从Akt/COX-2/P-gp信号通路探讨Sal-B逆转HCT-8/VCR细胞多药耐药的可能有效机制。[方法]1 MTT法鉴定HCT-8/VCR细胞的多药耐药性并检测Sal-B对HCT-8/VCR细胞的耐药逆转作用;2RT-PCR检测细胞中Akt、COX-2、MDR1基因表达情况;3Western blot检测细胞中Akt、p-Akt、COX-2、P-gp蛋白表达情况。[结果]HCT-8/VCR细胞有明显多药耐药性;Sal-B干预HCT-8/VCR细胞48h后,能增加其对不同化疗药物VCR、5-Fu、CDDP、TAXOL的敏感性,各化疗药物的半数抑制浓度IC50均明显下降(P<0.05);Sal-B干预HCT-8/VCR细胞48h后,使pAkt、COX-2、P-gp蛋白相对表达量均明显下调(P<0.05),而对Akt蛋白表达无影响;Sal-B组COX-2、P-gp基因相对表达量均明显减少(P<0.05),而对Akt基因表达无影响。[结论]Sal-B能有效改善HCT-8/VCR细胞的多药耐药性,其机制可能是通过抑制Akt磷酸化,下调COX-2的表达,进而减少MDR1/P-gp的表达。
[Objective] To explore the reversal effect of salvianolic acid B (Sal-B) on multidrug resistance of human colorectal cancer cell line HCT-8 / VCR and explore the relationship between Sal-B and Akt / COX-2 / P-gp signaling pathway Possible mechanism of reversing multidrug resistance in HCT-8 / VCR cells. [Methods] MTT was used to identify multidrug resistance in HCT-8 / VCR cells and to detect the reversal effect of Sal-B on HCT-8 / VCR cells. 2RT-PCR was used to detect the expression of Akt, COX-2 and MDR1 The expression of Akt, p-Akt, COX-2 and P-gp in the cells were detected by Western blot. [Results] HCT-8 / VCR cells had obvious multi-drug resistance. After HC-8 / VCR cells were treated by Sal-B for 48 hours, the sensitivity to different chemotherapeutic drugs VCR, 5-Fu, CDDP and TAXOL could be increased, (P <0.05). After HC-8 / VCR cells were treated by Sal-B for 48h, the relative expression of pAkt, COX-2 and P-gp protein were significantly decreased (P < 0.05), but had no effect on the expression of Akt protein. The relative expression of COX-2 and P-gp in Sal-B group was significantly decreased (P <0.05), but had no effect on Akt gene expression. [Conclusion] Sal-B can effectively improve the multidrug resistance of HCT-8 / VCR cells by down-regulating the expression of COX-2 and inhibiting the phosphorylation of Akt, thereby decreasing the expression of MDR1 / P-gp.