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热增强顺铂对实体艾氏癌的细胞毒性作用

Hyperthermic potentiation of cisplatin cytotoxicity on solid Ehrlich carcinoma.

作者信息

Ahmed M M, Khayyal M T, el-Merzabani M M

机构信息

Cancer Biology Department, National Cancer Institute, Cairo University, Egypt.

出版信息

Tumori. 1993 Aug 31;79(4):268-72. doi: 10.1177/030089169307900408.

DOI:10.1177/030089169307900408
PMID:8249181
Abstract

BACKGROUND

Hyperthermia produces marked effects on many biochemical parameters of tumor cells and has been reported to potentiate the effect of many drugs. We therefore evaluated the possible synergistic effect between hyperthermia and cisplatin against solid Ehrlich carcinoma. The study was based on the measurement of some biologic characteristics in tumor tissues, namely: DNA, RNA, and protein content and their rate of synthesis as parameters for nuclear damage; total lipids and cholesterol as parameters for membrane damage; acid-phosphatase and acid-ribonuclease as parameters for lysosomal damage; and tumor volume as a direct parameter for tumor growth.

METHODS

Treatment of solid Ehrlich carcinoma by hyperthermia at 43 degrees C for 30 min for 3 successive days produced a 41.5% decrease in tumor volume, as well as a significant decrease in nucleic acids, protein contents and their rate of synthesis, in total lipids and cholesterol, and in acid-phosphatase and acid-ribonuclease. Chemotherapeutic management of the tumor by 5 mg/kg x 3 of cisplatin alone showed a continuous increase in tumor volume but at a lower rate than that of the untreated control. However, when cisplatin was given 1 h prior to hyperthermia, the tumor volume was significantly decreased by 82.6%.

RESULTS

The effects observed on all the investigated parameter were intensified when cisplatin was combined with hyperthermia. The results obtained suggest that hyperthermia may enhance the penetration of cisplatin to its target site inside the tumor cells due to a membrane-damaging effect. The enhanced lethality of cisplatin on tumor cells may also be due to the inhibition of DNA repair processes by hyperthermia.

摘要

背景

热疗对肿瘤细胞的许多生化参数产生显著影响,并且据报道可增强许多药物的作用。因此,我们评估了热疗与顺铂联合对实体艾氏癌的可能协同作用。该研究基于对肿瘤组织中一些生物学特性的测量,即:DNA、RNA和蛋白质含量及其合成速率作为核损伤的参数;总脂质和胆固醇作为膜损伤的参数;酸性磷酸酶和酸性核糖核酸酶作为溶酶体损伤的参数;以及肿瘤体积作为肿瘤生长的直接参数。

方法

对实体艾氏癌进行连续3天、每天在43℃热疗30分钟的治疗,可使肿瘤体积减少41.5%,同时核酸、蛋白质含量及其合成速率、总脂质和胆固醇以及酸性磷酸酶和酸性核糖核酸酶均显著降低。单独使用5mg/kg×3的顺铂对肿瘤进行化疗处理,肿瘤体积持续增加,但增速低于未治疗的对照组。然而,当在热疗前1小时给予顺铂时,肿瘤体积显著减少了82.6%。

结果

当顺铂与热疗联合使用时,在所有研究参数上观察到的效果均增强。所得结果表明,由于膜损伤作用,热疗可能会增强顺铂向肿瘤细胞内靶位点的渗透。顺铂对肿瘤细胞致死性的增强也可能归因于热疗对DNA修复过程的抑制。

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