Human colon carcinoma LoVo/DX cells, which have been selected from parental LoVo for resistance to doxorubicin, express a typical multidrug resistant (MDR-1) phenotype. We have investigated whether phorbol 12-myristate 13-acetate (PMA) which often induces phenotypical changes in human tumor cells could, at the same time, modulate differentiation and sensitivity of LoVo/DX cells to doxorubicin. After 48 h exposure to 100 nM PMA, morphological changes became evident on LoVo/DX cells which showed elongated cytoplasm and dendritic-like structures: moreover immunocytochemical findings were suggestive of neuroendocrine-like differentiation. Under the same experimental conditions, LoVo/DX became sensitive to doxorubicin and showed enhanced intracellular drug-accumulation and reduced membrane expression of the 170 kD glycoprotein GP-170, which is the cellular product of the mdr1 gene. We conclude that pharmacological induction of tumor cell differentiation by PMA is paralleled by abrogation of drug resistance in a colon carcinoma MDR-1 cell line.

Phorbol 12-Myristate 13-Acetate (PMA) induces neuroendocrine-like differentiation and reverses doxorubicin-resistence of human colon-carcinoma cells in-vitro.

PEPE, Stefano;
1994-01-01

Abstract

Human colon carcinoma LoVo/DX cells, which have been selected from parental LoVo for resistance to doxorubicin, express a typical multidrug resistant (MDR-1) phenotype. We have investigated whether phorbol 12-myristate 13-acetate (PMA) which often induces phenotypical changes in human tumor cells could, at the same time, modulate differentiation and sensitivity of LoVo/DX cells to doxorubicin. After 48 h exposure to 100 nM PMA, morphological changes became evident on LoVo/DX cells which showed elongated cytoplasm and dendritic-like structures: moreover immunocytochemical findings were suggestive of neuroendocrine-like differentiation. Under the same experimental conditions, LoVo/DX became sensitive to doxorubicin and showed enhanced intracellular drug-accumulation and reduced membrane expression of the 170 kD glycoprotein GP-170, which is the cellular product of the mdr1 gene. We conclude that pharmacological induction of tumor cell differentiation by PMA is paralleled by abrogation of drug resistance in a colon carcinoma MDR-1 cell line.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3881195
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