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拓扑异构酶II抑制剂对阿霉素和依托泊苷耐药的小细胞肺癌亚系的细胞毒性作用

[Cytotoxic effect of topoisomerase II inhibitors against adriamycin- and etoposide-resistant small cell lung cancer sublines].

作者信息

Takigawa N, Ohnoshi T, Ueoka H, Yonei T, Kiura K, Tabata M, Kodani T, Kamei H, Segawa Y, Shibayama T

机构信息

Second Dept. of Medicine, Okayama University Medical School.

出版信息

Gan To Kagaku Ryoho. 1993 May;20(7):929-35.

PMID:8387762
Abstract

Using reverse transcription polymerase chain reaction, we determined mRNA expression of topoisomerase (topo) II alpha and beta in adriamycin- and etoposide-resistant small cell lung cancer sublines, SBC-3/ADM 100 and SBC-3/ETP. The expression of topo II alpha mRNA decreased substantially in SBC-3/ADM 100 and SBC-3/ETP as compared with the parent cell line, SBC-3; 0.71-fold in the former and 0.38-fold in the latter. Similarly, that of topo II beta mRNA decreased to an extent of 0.68-fold in SBC-3/ADM 100 and 0.28-fold in SBC-3/ETP as compared with the parent cell line. SBC-3/ADM 100 and SBC-3/ETP were highly resistant to topo II inhibitors such as daunorubicin, epirubicin, pirarubicin, mitoxantrone, and teniposide. However, SBC-3/ADM 100 showed a less resistance to aclarubicin, and SBC-3/ETP was as sensitive to the drug as was in the parent cell line. The resistance to topo II inhibitors excluding for aclarubicin might be partially explained by the decreased expression of topo II alpha and beta mRNA.

摘要

利用逆转录聚合酶链反应,我们测定了阿霉素和依托泊苷耐药的小细胞肺癌亚系SBC-3/ADM 100和SBC-3/ETP中拓扑异构酶(topo)IIα和β的mRNA表达。与亲本细胞系SBC-3相比,SBC-3/ADM 100和SBC-3/ETP中topo IIα mRNA的表达大幅下降;前者为0.71倍,后者为0.38倍。同样,与亲本细胞系相比,SBC-3/ADM 100中topo IIβ mRNA的表达下降至0.68倍,SBC-3/ETP中下降至0.28倍。SBC-3/ADM 100和SBC-3/ETP对拓扑异构酶II抑制剂如柔红霉素、表柔比星、吡柔比星、米托蒽醌和替尼泊苷具有高度抗性。然而,SBC-3/ADM 100对阿克拉霉素的抗性较低,SBC-3/ETP对该药物的敏感性与亲本细胞系相同。除阿克拉霉素外,对拓扑异构酶II抑制剂的抗性可能部分归因于topo IIα和β mRNA表达的降低。

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