Variable effects of sodium butyrate on the expression and function of the MDR 1 (P-glycoprotein) gene in colon carcinoma cell lines

✍ Scribed by Thomas O. Frommel; John S. Coon; Takashi Tsuruo; Igor B. Roninson

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: French
• Weight: 737 KB
• Volume: 55
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910550221

✦ Synopsis

Expression of the MDR I (P-glycoprotein) gene confers resistance to several classes of chemotherapeutic drugs (multi-drug resistance). Colon carcinomas frequently express high levels of MDR I mRNA and P-glycoprotein, presumably reflecting the origin of these tumors from MDRl -expressing normal colonic cells. In 4 colon carcinoma cell lines (SW 620, HCT-15, DLD-I, LS 180), MDRI expression was reported in an earlier study to be elevated after exposure to a differentiating agent, sodium butyrate (NaB). In one of these cell lines (SW 620), increased MDRl expression reportedly was not accompanied by a decrease in the accumulation or cytotoxicity of vinblastine, a P-glycoproteintransported drug, suggesting a possible functional abnormality of NaB-induced P-glycoprotein. We have re-examined the effect of NaB on MDRl /P-glycoprotein expression and function in the same colon carcinoma cell lines. NaB treatment induced differentiation-related changes and increased expression of MDRl mRNA in all 4 cell lines. A major increase in MDRl mRNA and P-glycoprotein expression was observed in only one line, SW 620. This increase, however, was accompanied by a commensurate increase in the activity of P-glycoprotein, indicating that the induced protein was fully functional. NaB treatment caused a relatively minor increase in MDRl mRNA expressed in the other 3 cell lines. Two of these lines showed a detectable increase in the P-glycoprotein expression and function, but in the third line (LS 180) P-glycoprotein was undetectable either before or after exposure to NaB. The magnitude of MDRl induction by NaB showed no apparent correlation with differentiation-related changes induced by this agent.