Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was found that the mechanism of anti-cancer drug resistance in anaplastic carcinoma of the thyroid was not explicable only in terms of expression of mdr1 and its gene product, P-glycoprotein. The multidrug resistance-associated protein (MRP), another member of the mdr gene family, may be involved in anti-cancer drug resistance of this carcinoma. The MRP expression was examined immunohistochemically in 8 cell lines and 73 thyroid cancer tissues; its frequency in anaplastic carcinoma (52%) was significantly higher than that in other thyroid cancer types.
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PMID:Expression of multidrug resistance-associated protein (MRP) in thyroid cancers. 765 21

ATP-binding cassette (ABC) transporters [P-glycoprotein and multidrug resistance (MDR)-associated proteins (MRPs)] confer MDR to tumor cells. In this work, we investigated doxorubicin resistance in three thyroid carcinoma cell lines. The effects of sodium butyrate (NaB) on doxorubicin-induced cytotoxicity and on transcription of three MDR genes were also studied. Thyroid cell lines established from anaplastic (8505C) and two poorly differentiated follicular (FTC 238 and FTC 133) cancers were cultured for 24 or 48 h in the presence of NaB (0, 0.25, 0.5 and 1 mM) alone or combined with increased doses of doxorubicin. Cytotoxicity was assessed using the MTT test. MDR1, MRP1 and MRP2 mRNA expression was studied by RT-PCR. After a 24- or 48-h incubation, doxorubicin alone induced cytotoxicity in the three cell lines. NaB significantly (p<0.0001) increased the doxorubicin-induced cytotoxicity. MRP1 transcripts were expressed in the three non-treated cell lines. MDR1 and MRP2 mRNAs were both present in 8505C, but absent in FTC 133 or FTC 238 cell lines, respectively. Treatment with NaB for 24 or 48 h induced no change in MRP1 and MRP2 levels, but increased MDR1 expression in 8505C and FTC 238 cell lines comparably to alkaline phosphatase activity. In conclusion, MRP1 and sometimes MDR1 and MRP2 are expressed in the tested cell lines. NaB potentiates doxorubicin-induced cytotoxicity independently of the ABC transporters. The combination of doxorubicin and NaB might have clinical implications for thyroid cancer therapy.
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PMID:Effect of sodium butyrate on doxorubicin resistance and expression of multidrug resistance genes in thyroid carcinoma cells. 1571 Nov 77