title: Phorbol 12-myristate 13-acetate (pma) induces neuroendocrine-like differentiation and reverses Doxorubicin-resistance of human colon-carcinoma cells in-vitro.
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.
authors.affiliation: UNIV FEDERICO 2,FAC MED,CATTEDRA ONCOL MED,VIA S PANSINI S,I-80131 NAPLES,ITALY. UNIV FEDERICO 2,FAC MED,CATTEDRA ANAT UMANA NORMALE,I-80131 NAPLES,ITALY.
authors.forename: P
authors.initials: P
authors.lastname: Correale
authors.forename: M
authors.initials: M
authors.lastname: Caraglia
authors.forename: S
authors.initials: S
authors.lastname: Pepe
authors.forename: B
authors.initials: B
authors.lastname: Ricciardi
authors.forename: C
authors.initials: C
authors.lastname: Barile
authors.forename: S
authors.initials: S
authors.lastname: Montagnani
authors.forename: R
authors.initials: R
authors.lastname: Pacelli
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.forename: P
authors.initials: P
authors.lastname: Tagliaferri