Human hepatoma cells rich in P-glycoprotein are sensitive to aclarubicin and resistant to three other anthracyclines.
Human hepatoma cells rich in P-glycoprotein are sensitive to aclarubicin and resistant to three other anthracyclines.
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富含P-糖蛋白的人肝癌细胞对阿昔霉素敏感，并且对其他三种蒽环类细胞抗性。
DOI：
10.1038/bjc.1996.621
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发表时间：
1996-12
影响因子：
8.8
通讯作者：
Rugstad, HE
中科院分区：
文献类型：
--
作者：
Lehne, G;DeAngelis, P;Clausen, OPF;Rugstad, HE
耐药是原发性肝癌化疗成功的主要障碍，多药耐药基因产物P-糖蛋白(P-gp)的高表达与多药外排转运蛋白的高表达有关。治疗原发性肝癌最有效的单一药物是蒽环类药物家族，但已知有几种蒽环类药物是Pgp的底物。在本研究中，我们利用富含Pgp的人肝癌细胞系HB8065/R和缺乏Pgp的亲本系HB8065/S，比较了四种蒽环类药物对细胞生长的抑制、细胞内蓄积和细胞外排的影响。HB8065/R细胞对阿克拉阿霉素(ACL)敏感，对表阿霉素(EPI)、阿霉素(DOX)和柔红霉素(DNR)高度耐药。SdZ PSC 833可促进EPI、DOX和DNR在HB8065/R细胞中的蓄积、外排和细胞毒作用，而ACL则无此作用。总而言之，在耐多药的人肝癌细胞系中，ACL显然不被Pgp转运，并保持其活性；这种特性可以用于临床目的。
Drug resistance is a major obstacle to successful chemotherapy of primary liver cancer, which is associated with high expression of the multidrug resistance (MDR) gene product P-glycoprotein (Pgp), a multidrug efflux transporter. The most effective single agents in treatment of primary liver carcinoma belong to the anthracycline family, yet several anthracyclines are known to be substrates for Pgp. In the present study, we compared four anthracyclines with respect to cell growth inhibition, intracellular accumulation and cellular efflux using the HB8065/R human hepatoma cell line which is rich in Pgp, and the Pgp-poor parental line HB8065/S. The anthracyclines were also administered in conjunction with the Pgp-modifying agents verapamil and SDZ PSC 833 to assess modulation of resistance. The HB8065/R cells were sensitive to aclarubicin (ACL) and highly resistant to epirubicin (EPI), doxorubicin (DOX) and daunorubicin (DNR). SDZ PSC 833 enhanced accumulation, decreased efflux and increased cytotoxicity of EPI, DOX and DNR in the HB8065/R cells, but none of these effects was seen with ACL. In conclusion, ACL is apparently not transported by Pgp and retains its activity in a multidrug-resistant human hepatoma cell line; such properties can be exploited for clinical purposes.
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影响因子：
158.5
作者：
CHAN, HSL;HADDAD, G;LING, V
通讯作者：
LING, V
影响因子：
45.3
作者：
CHAN, HSL;THORNER, PS;LING, V
通讯作者：
LING, V
DOI：
10.1073/pnas.83.20.7785
发表时间：
1986-10-01
影响因子：
11.1
作者：
HAMADA, H;TSURUO, T
通讯作者：
TSURUO, T
影响因子：
7.3
作者：
BACHUR, NR;STEELE, M;HILDEBRAND, RC
通讯作者：
HILDEBRAND, RC
影响因子：
6.2
作者：
BEPPU, T;OHARA, C;OGAWA, M
通讯作者：
OGAWA, M