Periostin Contributes to Cisplatin Resistance in Human Non-Small Cell Lung Cancer A549 Cells via Activation of Stat3 and Akt and Upregulation of Survivin

• Main Authors: Wenxia Hu, Pule Jin, Wei Liu
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2016-03-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Chemoresistance; Lung cancer; Periostin; Stat3 signaling; Therapeutic target
• Online Access: http://www.karger.com/Article/FullText/443068
• ISSN: 1015-8987; 1421-9778

Background/Aims: Periostin is upregulated in non-small cell lung cancer (NSCLC). This study was done to explore the function of periostin in the development of cisplatin (CDDP) resistance in NSCLC. Methods: The effects of overexpression or knockdown of periostin on CDDP sensitivity was examined in A549 cells. The involvement of signal transducer and activator of transcription 3 (Stat3) and Akt signaling in the action of periostin was checked. The in vivo effect of periostin silencing on CDDP susceptibility was determined in a mouse xenograft model. Results: Periostin was significantly upregulated in CDDP-resistant A549 cells, compared to parental controls. Overexpression of periostin rendered A549 cells more resistant to CDDP-induced apoptosis and enhanced Stat3 and Akt phosphorylation and survivin expression. Periostin-mediated protection against CDDP-induced apoptosis was compromised by downregulation of survivin. Furthermore, knockdown of periostin re-sensitized CDDP-resistant A549 cells to CDDP. After CDDP treatment, greater volume reduction was observed in periostin-silenced xenograft tumors than in control tumors, which was accompanied by reduced levels of phosphorylated Stat3 and survivin in periostin-depleted tumors. Conclusion: In conclusion, periostin promotes CDDP resistance in NSCLC cells largely through activation of Stat3 and Akt and upregulation of survivin and thus represents a promising target for overcoming CDDP resistance.