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

Abstract

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.

• Authors: Sui-qing Cai, Li-rong Chen, Min Zheng
• Journal: Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences (Zhejiang Da Xue Xue Bao Yi Xue Ban) Vol. 35 Issue 2 Pg. 182-8 (03 2006) ISSN: 1008-9292 [Print] China
• PMID: 16610086 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Acitretin

Topics

• Acitretin (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (pathology)
• Cell Line, Tumor
• Humans
• Signal Transduction (drug effects)
• Skin Neoplasms (pathology)