摘要
目的探讨两种新型西地那非同系物对人乳腺癌MCF-7/ADR细胞耐阿霉素的逆转作用。方法采用GENMED磷酸二酯酶5(PDE5)活性酶测定试剂盒检测两种同系物对5型磷酸二酯酶(PDE5)的抑制作用,用MTT法检测西地那非、西地那非同系物、阿霉素以及西地那非同系物与阿霉素联合作用对人乳腺癌耐药细胞MCF-7/ADR和敏感株MCF-7的抑制率及IC50值,运用Western blot检测P-gp蛋白的表达。结果两种同系物与西地那非相比具有较低的PDE5抑制活性;10μmol·L-1的两种西地那非同系物对MCF-7/ADR细胞耐药性的逆转倍数分别是6.36和5.58,20μmol·L-1的两种西地那非同系物对MCF-7/ADR细胞耐药性的逆转倍数分别是11.83和13.47;两种同系物作用对P-gp蛋白的表达无明显影响。结论两种新型西地那非同系物具有较低的PDE5抑制活性,一定浓度的西地那非同系物可显著逆转MCF-7/ADR细胞对阿霉素的耐药。
Objective To explore the reversal effects of XDNF1-0425 and XDNF8-0113 on Doxorubicin resistance in human breast cancer cell line MCF-7/ADR in vitro. Methods GENMED phosphodiesterase5（PDE5） activity assay kit was used to detect the inhibition of two kinds of sildenafil homologues to PDE5. MTT assay was used to determine the cell growth inhibiting ratio of human breast cancer cell line MCF-7 and MCF-7/ADR cells after treated by Sildenafil, XDNF1-0425, XDNF8-0113, Doxorubici（DOX） or Doxorubici（DOX） plus Sildenafil homologues. Further more, figured out each inhibitive concentration 50（IC50） of DOX. The expression of P-gp was determined with Western blot. Results It showed that the two kinds of homologues（XDNF1-0425 and XDNF1-0113） have weaker inhibitory activity of PDE5 than the sildenafil. The sensitivity of MCF-7/ADR to DOX was significantly increased by XDNF1-0425 and XDNF1-0113 in a dose-dependent manner（P0.05）. The sensitivity of MCF-7/ADR to DOX was significantly increased with a reversal fold of 6.36/5.58 by 10 μmol·L^-1XDNF1-0425/XDNF1-0113, and even increased with a reversal fold of 11.83/13.47 by 20 μmol·L^-1XDNF1-0425/XDNF1-0113. Western blot results showed that both homologues had no effect on the expression of protein. Conclusion The two Sildenafil homologues have a weaker inhibitory activity. Certain concentration of Sildenafil homologues could effectively reverse Doxorubicin resistance in human breast cancer cell line MCF-7/ADR in vitro.
出处
《肿瘤药学》
CAS
2014年第1期26-31,共6页
Anti-Tumor Pharmacy
基金
广东省高等学校大学生创新实验项目(10573120033)
广州市国际区域科技合作项目(2011J5200017)
