He Q Y, Meng F H, Zhang H Q
Naval Medical Research Institute, Shanghai, China.
Zhongguo Yao Li Xue Bao. 1996 Mar;17(2):179-81.
To study whether tetrandrine (Tet) and dauricine (Dau) can reduce doxorubicin (Dox) resistance in the harringtonine (Har)-resistant human leukemia cells.
The drug cytotoxities were determined by counting cell numbers and colony formation. Cell cycle phases were assayed by flow cytometry, Dox contents were quantified by Dox fluorescence.
The non-cytotoxic concentrations of Tet and Dau potentiated the growth-inhibitory actions of Dox in the Har-resistant HL60 cells. The colony formation effiencies were reduced from 60% by Dox to 0.2% by Tet + Dox and 9.2% by Dau + Dox. Retardation of the G2M phase cells was increased. But Tet and Dau did not potentiate Dox cytotoxities in the sensitive HL60 cells. Dox accumulation in the Har-resistant HL60 cells treated by Tet was increased.
Dox resistance in the Har-resistant HL60 cells treated by Tet or Dau was reduced, due to the increase of Dox accumulation in the cells. One of the mechanisms of multidrug resistance in tumor cells is overexpression of cell membrane glycoproteins, termed P-glycoprotein (PGP). PGP pumps antitumor drugs out of tumor cells, causing drug resistance. Calcium antagonists and some calmodulin inhibitors such as verapamil, nifedepine, trifluorapine have effect on reversion of drug resistance, binding directly to PGP, but side effect of them is intolerable in clinical use. So searching for other potentiators to overcome drug resistance may be another avenue. Tetrandrine (Tet) effectively circumvented the resistance of Chinese hamster ovary cells to doxorubicin (Dox). Dauricine (Dau) is a bisbenzylisoquinoline alkaloid from Stephaia tetrandra. In this paper we studied whether Tet and Dau could reduce Dox resistance in the harringtonine (Har)-resistant human leukemia 60 (HL60) cells.
研究粉防己碱（Tet）和蝙蝠葛碱（Dau）是否能降低高三尖杉酯碱（Har）耐药的人白血病细胞对阿霉素（Dox）的耐药性。
通过细胞计数和集落形成来测定药物细胞毒性。采用流式细胞术检测细胞周期阶段，用Dox荧光法定量Dox含量。
Tet和Dau的无细胞毒性浓度增强了Dox对Har耐药HL60细胞的生长抑制作用。集落形成效率从Dox单独作用时的60%分别降至Tet+Dox作用时的0.2%和Dau+Dox作用时的9.2%。G2M期细胞阻滞增加。但Tet和Dau对敏感HL60细胞的Dox细胞毒性无增强作用。Tet处理的Har耐药HL60细胞中Dox蓄积增加。
Tet或Dau处理可降低Har耐药HL60细胞对Dox的耐药性，原因是细胞内Dox蓄积增加。肿瘤细胞多药耐药的机制之一是细胞膜糖蛋白（称为P-糖蛋白，PGP）过度表达。PGP将抗肿瘤药物泵出肿瘤细胞，导致耐药。钙拮抗剂和一些钙调蛋白抑制剂如维拉帕米、硝苯地平、三氟拉嗪对耐药逆转有作用，它们直接与PGP结合，但临床使用时其副作用难以耐受。因此寻找其他增效剂来克服耐药性可能是另一条途径。粉防己碱（Tet）有效地克服了中国仓鼠卵巢细胞对阿霉素（Dox）的耐药性。蝙蝠葛碱（Dau）是从粉防己中提取的双苄基异喹啉生物碱。本文研究了Tet和Dau是否能降低高三尖杉酯碱（Har）耐药的人白血病60（HL60）细胞对Dox的耐药性。
