Involvement of insulin-like growth factor-I secretion and all-trans-retinoic acid-induced decrement in viability in MCF-7 cells

Riferimento: 
Chemotherapy. 2011;57(1):17-26.
Autori: 
Oh YI, Kim JH, Kang CW.
Fonte: 
Chemotherapy. 2011;57(1):17-26.
Anno: 
2011
Azione: 
Il fattore di crescita insulino-simile 1 (IGF-I) gioca un ruolo importante nell'azione dell'acido all-trans retinoico (RA) e che la soppressione di IGF-I è implicato nella RA-inibizione della vitalità cellulare nella linea cellulare MCF-7.
Target: 
IGF-1 – RA/adenocarcinoma mammario.

BACKGROUND/AIM:
Insulin-like growth factor-I (IGF-I) is associated with survival, apoptosis and proliferation in MCF-7 cells. All-trans-retinoic acid (RA) is used as a cancer therapeutic, but the use of RA in cancer therapy is limited by the unpredictable resistance of cancer cells to drug action. Furthermore, the relationship of IGF-I with RA-induced decrement in cell viability has yet to be elucidated.
MATERIALS AND METHODS:
MCF-7 cells were grown as confluent monolayers. To demonstrate the signaling pathways and roles of IGF-I, we suppressed endogenous target IGF-I with specific small interfering RNA treatment. Protein kinase C-δ and insulin receptor substrate 1 (IRS-1) protein levels were analyzed by Western blot. Radioimmunoassays were used to assess the concentration of endogenous IGF-I, and RT-PCR was used to assess IGF-I mRNA expression. Cell viability was analyzed with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay.
RESULTS:
We showed that RA treatment resulted in a dose- and time-dependent decrease in the secretion and synthesis of IGF-I. Subsequently, we found that suppression of IGF-I and IRS-1 protein decreased cell viability. In contrast, suppression of protein kinase C-δ and stimulation of IGF-I protected cells from RA-induced decrement in cell viability. The combination of RA treatment with IGF-I or IRS-1 small interfering RNA resulted in an additive decrease in cell viability. CONCLUSION:
These results indicate that IGF-I plays an important role in the effect of RA and that suppression of IGF-I is implicated in the RA-induced inhibition of cell viability in MCF-7 cells.

Sostanze: