[Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431].

OBJECTIVE

To study the effects of Acitretin on growth inhibition and apoptosis of epidermoid carcinoma cell line A431 and its molecular mechanisms.

METHODS

A431 cells were treated with Acitretin at the concentration of 10(-5)mol/L in different time intervals. The inhibition of cell growth was determined by MTT method, morphological changes were observed by electron microscopy, apoptosis was assessed by flow cytometry and Annexin-V staining. The mRNA expression levels of STAT3, cyclinD1 and p42/44MAPK were detected by reverse transcriptase polymerase chain reaction (RT-PCR). The protein expression levels of P-STAT3 and CyclinD1 were observed by Western blot in A431 cells.

RESULT

(1)Acitretin inhibited the growth of A431 cells in vitro in a dose-and time-dependent manner. Morphological changes revealed characteristics of cell apoptosis. Flow cytometry showed more sub-G(1) phase in A431 cells and more cells positively stained with Annexin-V. (2)Acitretin significantly inhibited the expression of STAT3 and CyclinD1 mRNA in A431 cells in vitro in a time-dependent manner(P<0.05). The p-STAT3 and CyclinD1 protein levels were down regulated. The Acitretin could also down regulate the p42/4MAPK mRNA in A431 cells. (3) After incubation with Acitretin, the mRNA level of CyclinD1 in A431 cells was positively correlated with that of STAT3(p<0.05). The protein level of CyclinD1 was also positively correlated with that of p-STAT3(p<0.05). However, there was no correlation between Mrna levels of CyclinD1 and p42/44MAPK.

CONCLUSION

(1)Acitretin plays an inhibitory role in the tumor cell growth and induces the cell apoptosis in A431 cells. (2)The regulation of the Jak/STAT3 signaling pathway may play an important role in inducing growth inhibition and apoptosis by Acitretin in A431 cells.