新型氟奋乃静类似物作为人淋巴细胞培养物中P-糖蛋白的抑制剂
New fluphenazine analogues as inhibitors of P-glycoprotein in human lymphocyte cultures.
作者信息
Jaszczyszyn Agata, Gąsiorowski Kazimierz, Swiątek Piotr, Malinka Wiesław, Cieślik-Boczula Katarzyna, Petrus Joanna, Czarnik-Matusewicz Bogusława
机构信息
Department of Basic Medical Sciences, Wrocław Medical University, Wrocław, Poland.
出版信息
Contemp Oncol (Pozn). 2012;16(4):332-7. doi: 10.5114/wo.2012.30063. Epub 2012 Sep 29.
AIM OF THE STUDY
To evaluate the inhibitory effect of 17 new analogues of FPh on the Pgp transport function, by estimation of the rhodamine 123 (Rod-123) accumulation inside cultured lymphocytes.
MATERIAL AND METHODS
Lymphocyte were cultured in the presence of a lectin (PHA; 2%, v/v), incubated with benzo[α]pyrene (B[α]P; 7.5 µM, 48 h) to induce genotoxic damage and to increase Pgp expression in the cells. Lymphocytes cultured without the tested compounds were considered as controls.
RESULTS
It was established that 10 analogues of FPh, among 17 tested, significantly increased Rod-123 accumulation in lymphocytes at the concentration of 10 µM. As compared to the control cultures the Pgp transport function was the most strongly inhibited by 1a, 1b, 1d, 3f, 3h and 3i analogues (approximately by 25%).
CONCLUSIONS
FPh analogues 1a, 1b, 1d, 3f, 3h and 3i should be further studied as promising candidates for adjuvant cancer chemotherapeutics.
研究目的
通过评估罗丹明123（Rod-123）在培养淋巴细胞内的蓄积情况，来评价17种新型FPh类似物对Pgp转运功能的抑制作用。
材料与方法
淋巴细胞在凝集素（PHA；2%，v/v）存在的情况下进行培养，与苯并[a]芘（B[a]P；7.5 µM，48小时）共同孵育，以诱导遗传毒性损伤并增加细胞中Pgp的表达。未添加受试化合物培养的淋巴细胞作为对照。
结果
已确定，在17种受试的FPh类似物中，有10种在浓度为10 µM时能显著增加淋巴细胞内Rod-123的蓄积。与对照培养物相比，1a、1b、1d、3f、3h和3i类似物对Pgp转运功能的抑制作用最强（约25%）。
结论
FPh类似物1a、1b、1d、3f、3h和3i作为辅助癌症化疗药物的有前景的候选物，应进一步研究。
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