CAJ | 학술논문

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 Westernblot 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。
목적：탐토량충신형서지나비동계물대인유선암 MCF-7/ADR 세포내아매소적역전작용。방법채용 GENMED 린산이지매5（PDE5）활성매측정시제합검측량충동계물대5형린산이지매（PDE5）적억제작용，용 MTT 법검측서지나비、서지나비동계물、아매소이급서지나비동계물여아매소연합작용대인유선암내약세포 MCF-7/ADR 화민감주 MCF-7적억제솔급 IC50치，운용 Westernblot 검측 P-gp 단백적표체。결과량충동계물여서지나비상비구유교저적 PDE5억제활성；10μmol·L-1적량충서지나비동계물대 MCF-7/ADR 세포내약성적역전배수분별시6.36화5.58，20μmol·L-1적량충서지나비동계물대 MCF-7/ADR 세포내약성적역전배수분별시11.83화13.47；량충동계물작용대 P-gp 단백적표체무명현영향。결론량충신형서지나비동계물구유교저적 PDE5억제활성，일정농도적서지나비동계물가현저역전 MCF-7/ADR 세포대아매소적내약。
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 inhibi-tive 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 (P<0.05). The sensitivity of MCF-7/ADR to DOX was significantly increased with a reversal fold of 6.36/5.58 by 10 μmol·L-1 XDNF1-0425/XDNF1-0113, and even increased with a reversal fold of 11.83/13.47 by 20 μmol·L-1 XDNF1-0425/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.