In vitro modulation of multidrug resistance by pregnane steroids and in vivo inhibition of tumour development by 7α-OBz-11α(R)-OTHP-5β-pregnanedione in K562/R7 and H295R cell xenografts

被引：4

作者：

Alameh, Ghina ^{[1
]}

Emptoz-Bonneton, Agnes ^{[1
,2
]}

de Ravel, Marc Rolland ^{[1
,3
]}

Matera, Eva L. ^{[3
]}

Mappus, Elisabeth ^{[1
]}

Balaguer, Patrick ^{[4
]}

Rocheblave, Luc ^{[1
,5
]}

Lomberget, Thierry ^{[1
,5
]}

Dumontet, Charles ^{[3
]}

Le Borgne, Marc ^{[5
]}

Pugeat, Michel ^{[1
,2
]}

Grenot, Catherine ^{[1
]}

Cuilleron, Claude Y. ^{[1
]}

机构：

[1] Univ Lyon 1, Univ Lyon, ISPB Fac Pharm, 8 Ave Rockefeller, F-69373 Lyon, France

[2] Hosp Civils Lyon, Federat Endocrinol Pole Est, Lyon, France

[3] Univ Claude Bernard Lyon 1, Ctr Rech Cancerol Lyon, INSERM, Ctr Leon Berard, Lyon, France

[4] Univ Montpellier, Inst Rech Cancerol Montpellier, Montpellier, France

[5] Univ Claude Bernard Lyon 1, Univ Lyon, Dept Bioact Mol & Med Chem, Fac Pharm ISPB, 8 Ave Rockefeller, F-69373 Lyon, France

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2019年 / 34卷 / 01期

关键词：

Multidrug resistance; P-glycoprotein; non-steroidogenic and steroidogenic cell lines; pregnane modulators; xenografts; P-GLYCOPROTEIN; PROGESTERONE; DOXORUBICIN; IDENTIFICATION; REVERSAL; GROWTH; CANCER;

D O I：

10.1080/14756366.2019.1575825

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Synthetic progesterone and 5 alpha/beta-pregnane-3,20-dione derivatives were evaluated as in vitro and in vivo modulators of multidrug-resistance (MDR) using two P-gp-expressing human cell lines, the non-steroidogenic K562/R7 erythroleukaemia cells and the steroidogenic NCI-H295R adrenocortical carcinoma cells, both resistant to doxorubicin. The maximal effect in both cell lines was observed for 7 alpha-O-benzoyloxy,11 alpha(R)-O-tetrahydropyranyloxy-5 beta-pregnane-3,20-dione 4. This modulator co-injected with doxorubicin significantly decreased the tumour size and increased the survival time of immunodeficient mice xenografted with NCI-H295R or K562/R7 cells.

引用

页码：684 / 691

页数：8

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