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Ayako Fujiwara
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-068 - Effects of Pirfenidone Targeting EMT and Tumor-Stroma Interaction as Novel Treatment for Non-Small Cell Lung Cancer (ID 8983)
09:30 - 16:00 | Presenting Author(s): Ayako Fujiwara
- Abstract
Background:
Epithelial-to-mesenchymal transition (EMT) is related to the malignant behavior of cancer. Interaction between cancer-associated fibroblasts (CAFs) and tumor cells has been shown to increase tumor cell survival via several pathways including EMT. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis and one of its functions may be to inhibit fibrotic EMT. We evaluated the effects of PFD on EMT using non-small cell lung cancer (NSCLC) cells, as well as interactions between CAFs and NSCLC cells in vitro and in vivo.
Method:
NSCLC cells (A549, NCI-H358) were used to evaluate the effects of PFD on EMT. Primary human fibroblasts obtained from tumors as well as normal tissues were isolated from surgically resected lungs of three patients with lung cancer, and defined as CAFs and LNFs, respectively. The effects of PFD on activation of CAFs and LNFs were determined by analyzing the expression of hallmarks of fibroblast activation and pro-inflammatory markers. In addition, the impact of PFD on interactions between NSCLC cells and CAFs was also determined in vitro using a co-culture technique, as well as in vivo using co-implantation of those cells.
Result:
PFD significantly inhibited TGF-β1-induced EMT in NSCLC cells, and also the activation levels of α-SMA and collagen I, as well as cytokine productions of IL-6 and TGF-β1 by LNFs and CAFs. qRT-PCR results showed that the median diminution rates for three patients by PFD were 0.303 in LNFs and 0.69 in CAFs for α-SMA, and 0.316 in LNFs and 0.627 in CAFs for collagen I. Medium conditioned with LNFs or CAFs significantly induced EMT in NSCLC cells, while pretreatment of LNFs or CAFs with PFD inhibited the EMT change in NSCLC cells. In vivo findings showed that co-implantation of CAFs promoted tumor progression, which was suppressed by PFD via inhibition of EMT and stroma outgrowth. Immunohistological analysis showed that the Ki67 labelling index was higher in the co-implantation group than in the control group. Administration of PFD reduced the Ki67 labelling index by 27.1% in A549 tumors and 27.0% in NCI-H358 tumors in the co-implantation group. PFD also decreased α-SMA positive area with restoration of E-cadherin expression.
Conclusion:
Our findings suggest that PFD inhibits EMT and fibroblast activity, as well as cross-talk between cancer cells and fibroblasts. PFD may have great potential as a novel agent with a wide variety of actions for treatment of NSCLC.
