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

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Abstract
Expression of the MDRI (P‐glycoprotein) gene confers resistance to several classes of chemotherapeutic drugs (multi‐drug resistance). Colon carcinomas frequently express high levels of MDRI mRNA and P‐glycoprotein, presumably reflecting the origin of these tumors from MDRI ‐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 MDR I expression reportedly was not accompanied by a decrease in the accumulation or cytotoxicity of vinblastine, a P‐glycoprotein‐transported drug, suggesting a possible functional abnormality of NaB‐induced P‐glycoprotein. We have re‐examined the effect of NaB on MDRI /P‐glycoprotein expression and function in the same colon carcinoma cell lines. NaB treatment induced differentiation‐related changes and increased expression of MDRI mRNA in all 4 cell lines. A major increase in MDRI 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 MDRI 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 MDRI induction by NaB showed no apparent correlation with differentiation‐related changes induced by this agent.
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