Abstract
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance. Furthermore, it was also observed that IL-11 induced STAT3 phosphorylation and increased anti-apoptotic protein Bcl-2 and Survivin expression in cancer cells. The effect could be abrogated by suppressing STAT3 phosphorylation or silencing IL-11Rα expression in cancer cells. In conclusion, chemotherapy-induced IL-11 upregulation in CAF promotes lung adenocarcinoma cell chemoresistance by activating IL-11R/STAT3 anti-apoptotic signaling pathway.
Highlights
In the study, we found IL-11 facilitated lung cancer cell chemoresistance via IL-11R/STAT3 signaling pathway which promoted anti-apoptosis protein activation
Cancer-associated fibroblasts rich lung adenocarcinoma were more resistant to cisplatin-based chemotherapy
To investigate the relationship between cancer-associated fibroblasts (CAF) and chemoresistance of lung adenocarcinoma patients, a total of 55 clinical tumor tissue samples were collected from lung adenocarcinoma patients who received cisplatin-based chemotherapy
Summary
We found IL-11 facilitated lung cancer cell chemoresistance via IL-11R/STAT3 signaling pathway which promoted anti-apoptosis protein activation. Results Cancer-associated fibroblasts rich lung adenocarcinoma were more resistant to cisplatin-based chemotherapy. Statistical analysis showed a correlation between CAF and responses to cisplatin-based chemotherapy in lung adenocarcinoma patients.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have