Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metallothionein (MT) proteins are associated with resistance to the toxic effects of heavy metals, chemotherapeutic drugs, and alkylating agents. It has been suggested that MT may mediate both resistance to toxic agents and cellular metal homeostasis. To study the role of MT, we obtained cells expressing a range of MT levels in the absence of heavy metal induction. We cotransfected the eukaryotic G418 resistance vector pSV2neo and mouse MT-1 cDNA in a pBR322 vector into Chinese hamster ovary cells. Of 200 transfected clonal cell populations, five had constitutive MT expression ranging from 31 to 87 ng of MT/mg of protein. All five populations had increased resistance to cadmium but were less resistant to cisplatin than control cells. On the other hand, the level of foreign MT expression correlated well with the degree of cisplatin resistance among the five clones. Resistance to ionizing radiation and growth rate in the absence of drug or radiation treatment were not affected. However, transfected MT gene expression inhibited the ability of Chinese hamster ovary cells to form colonies in the absence of toxic drug treatment (r = -0.95). The perturbation of cisplatin sensitivity after genetic alteration of MT expression indicates a role for MT in drug resistance: however, the fact that transfected MT gene expression decreased rather than increased drug resistance and decreased plating efficiency in the absence of drug implies that the role of MT may not be one of simply "scavenging" toxic molecules. These data suggest a role for MT in homeostatic cellular processes that, when distributed by transfection of active MT genes, have an effect on cellular drug resistance.
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PMID:Altered cisplatin and cadmium resistance and cell survival in Chinese hamster ovary cells expressing mouse metallothionein. 834 Dec 78

Metallothionein-I (MT-I) gene was inserted into EcoRI site by using pSV2-neo plasmid vector. Recombiant plasmid was transfected into HeLa cells by DNA-calcium phosphate precipitation technique. MT-I expression colones were growing in medium including G418. The amount of MT-I expression in transfected cells was found 2.6 times higher than that of non-transfected ones. In order to observe the relationship between the expression of MT-I gene in cells and drug resistance, cells were treated with different concentrations of cisplatin and adriamycin respectively. The results indicated that cisplatin (0.1 mumol/ml) inhibited the growth of both transfected and non-transfected cells. The inhibitory rates were 34% and 82% respectively(P < 0.05). IC50(50% inhibitory concentration for cell growing) was 0.144 mumol/ml and 0.061 mumol/ml and the ratio of them was 2.36: 1 after the treatment of cisplatin 72 h later. The cells were treated with adriamycin 72 h later, the inhibitory rates of transfected and non-transfected cells were 18% and 25% separately. The rates showed no significant difference (P > 0.05). The results indicated that MT was related to drug resistance of tumor cells.
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PMID:[Effects of the expression of mouse metallothionein-I gene in human HeLa cell line on drug resistance]. 1252 Sep 15