[Modification of the response to paclitaxel of human differentiated colon cancer line after long-term treatment at very low dose].
Taxoids (paclitaxel, Taxol and docetaxel, Taxotere), drugs which stabilize microtubules, demonstrate marked activity against ovarian, brain and lung cancer. We investigated, on the human colon adenocarcinoma HT29-D4 cell line, firstly the effects of taxoids in function of the differentiation state and secondly the effects of a low dose of paclitaxel on the differentiation process. The cellular parameters studied were microtubular network, cell cycle and cell tubulin content. Undifferentiated cells treated with paclitaxel or docetaxel (10-100 nM) classically induced bundles in interphasic cells and pseudoasters in mitotic cells, arrest in cell cycle in G2M and increase in tubulin content. Inversely, no modification was observed in differentiated cells after similar taxoid treatment. Long-term low-dose pretreatment of differentiated cells restitutes some sensitivity to taxoids since these cells become responsive to further taxoid treatment, as reflected by modifications of the microtubule network.
Carles
G
G
Faculté de pharmacie, CNRS URA, Marseille, France.
Braguer
D
D
Rognoni
J B
JB
Roccabianca
M
M
Marvaldi
J
J
Briand
C
C
D000230:Adenocarcinoma / Q000188:drug therapy*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
Modification de la réponse au paclitaxel d'une lignée cancéreuse humaine de côlon différenciée après traitement continu à très faible dose.