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高迁移率族蛋白2 cDNA转染的人肺癌细胞中顺铂敏感性的增强

Enhancement of cisplatin sensitivity in high mobility group 2 cDNA-transfected human lung cancer cells.

作者信息

Arioka H, Nishio K, Ishida T, Fukumoto H, Fukuoka K, Nomoto T, Kurokawa H, Yokote H, Abe S, Saijo N

机构信息

Pharmacology Division, National Cancer Center Research Institute, Tokyo.

出版信息

Jpn J Cancer Res. 1999 Jan;90(1):108-15. doi: 10.1111/j.1349-7006.1999.tb00673.x.

DOI:10.1111/j.1349-7006.1999.tb00673.x
PMID:10076573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5925981/
Abstract

To elucidate the role of high mobility group 2 protein (HMG2) in cis-diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a human HMG2-transfected human non-small cell lung cancer cell line, PC-14/HMG2. The HMG2 mRNA expression level was approximately twice those of parental PC-14 and mock-transfected PC-14/CMV. Gel mobility shift assay revealed a CDDP-treated DNA-protein complex in the nuclear extract of PC-14/HMG2, which was not found in the extracts of PC-14 and PC-14/CMV. This complex formation was subject to competition by CDDP-treated non-specific salmon sperm DNA, indicating that ectopic HMG2 recognizes CDDP-damaged DNA. PC-14/HMG2 showed more than 3-fold higher sensitivity to CDDP than PC-14 and PC-14/CMV. The intracellular platinum content of PC-14/HMG2 after exposure to 300 microM CDDP was 1.1 and 1.5 times that of PC-14 and PC-14/CMV, respectively. Cellular glutathione levels were not different in these cell lines. Repair of DNA interstrand cross-links determined by alkaline elution assay was decreased in PC-14/HMG2. These results suggest that HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA lesion induced by CDDP.

摘要

为阐明高迁移率族蛋白2（HMG2）在顺二氯二氨铂（II）（顺铂，CDDP）敏感性中的作用，我们构建了转染人HMG2的人非小细胞肺癌细胞系PC-14/HMG2。HMG2 mRNA表达水平约为亲代PC-14和空载体转染的PC-14/CMV的两倍。凝胶迁移率变动分析显示，在PC-14/HMG2的核提取物中存在经CDDP处理的DNA-蛋白质复合物，而在PC-14和PC-14/CMV的提取物中未发现。这种复合物的形成受到经CDDP处理的非特异性鲑鱼精DNA的竞争，表明异位表达的HMG2识别CDDP损伤的DNA。PC-14/HMG2对CDDP的敏感性比PC-14和PC-14/CMV高3倍以上。暴露于300 microM CDDP后，PC-14/HMG2的细胞内铂含量分别是PC-14和PC-14/CMV的1.1倍和1.5倍。这些细胞系中的细胞谷胱甘肽水平没有差异。通过碱性洗脱分析测定，PC-14/HMG2中DNA链间交联的修复减少。这些结果表明，HMG2可能通过抑制CDDP诱导的DNA损伤修复来增强细胞对CDDP的敏感性。

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