Enhanced stability of microtubules contributes in the development of colchicine resistance in MCF-7 cells.
Biochem Pharmacol
; 132: 38-47, 2017 05 15.
Article
em En
| MEDLINE
| ID: mdl-28242250
ABSTRACT
Understanding the mechanism of resistance to tubulin-targeted anticancer drugs is important for improved chemotherapy. In this work, a colchicine-resistant MCF-7 cell line (MCF-7Col30) was generated by the gradual increment of colchicine treatment and the MCF-7Col30 showed â¼8-fold resistance towards colchicine. MCF-7Col30 cells showed â¼2.5-fold resistance against microtubule depolymerizing agents, vinblastine, and nocodazole. In contrast, it displayed more sensitivity towards paclitaxel, a microtubule-polymerizing agent. MCF-7 and MCF-7Col30 cells showed similar sensitivity towards cisplatin. Further, the level of P-glycoprotein did not increase in MCF-7Col30 cells. MCF-7Col30 cells resisted the microtubule depolymerizing effects of colchicine. The time-lapse imaging of individual microtubules in live cells showed that the dynamics of microtubules in MCF-7Col30 cells was suppressed as compared to the parent MCF-7 cells. The levels of tubulin acetylation and glutamylation increased in MCF-7Col30 cells than the parent MCF-7 cells suggesting that microtubules are stabilized in MCF-7Col30 cells. Interestingly, the level of ßIII tubulin was increased by 2.3 folds whereas that of ßII and ßIV tubulin was decreased by 55 and 150%, respectively in MCF-7Col30 cells. The results suggested that the changes in the level of ß-tubulin isoforms and the post-translational modifications of microtubules altered the stability and dynamics of microtubules and contributed to the development of colchicine-resistance in MCF-7 cells.
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Base de dados:
MEDLINE
Assunto principal:
Colchicina
/
Microtúbulos
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article