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Research ArticleExperimental Studies

Induction of Apoptosis and Inhibition of EGFR/NF-κB Signaling Are Associated With Regorafenib-sensitized Non-small Cell Lung Cancer to Cisplatin

JENG-YUAN WU, YUEH-SHAN WENG, YI-CHOU CHIOU, FEI-TING HSU and I-TSANG CHIANG
In Vivo September 2021, 35 (5) 2569-2576; DOI: https://doi.org/10.21873/invivo.12539
JENG-YUAN WU
1Department of Thoracic Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, R.O.C.;
2School of Medicine, Tzu Chi University, Hualien, Taiwan, R.O.C.;
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YUEH-SHAN WENG
3Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C;
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YI-CHOU CHIOU
4Chest Medicine Department, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.;
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FEI-TING HSU
3Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C;
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I-TSANG CHIANG
5Department of Radiation Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.;
6Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.;
7Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
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  • For correspondence: 106883{at}ctust.edu.tw
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    Figure 1.

    Induction of cytoxicity and inactivation of EGFR/NF-κB was found in regorafenib combination with cisplatin in A549 cells. A549 cells were treated with (A) 0-30 μM regorafenib, (B) 0-25 μM cisplatin, (C) 10 μM regorafenib combined with 0-25 μM cisplatin, (D) 0-5 μM QNZ, (E) 1 μM QNZ combined with 0-25 μM cisplatin and (F) 10 μM erlotinib combined with 0-25 μM cisplatin for 48 h and assayed by MTT. (G-H) The expression pattern and quantification results of EGFR and NF-κB phosphorylation are shown. a1p<0.05, a2p<0.01, a3p<0.005 vs. 0 μM of treatment; b2p<0.01, b3p<0.005 vs. 10 μM regorafenib, 1 μM QNZ or 10 μM erlotinib; c1p<0.05 vs. 15 μM cisplatin).

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    Figure 2.

    Synergistic activation of death receptor of apoptosis and mithochondria-dependent apoptosis were found in regorafenib combined with cisplatin in A549 cells. A549 cells were treated with 10 μM regorafenib, 15 μM cisplatin and their combination for 48 h. The activation patterns and quantification results of (A) caspase-3, (B) caspase-8, and (C) caspase-9 were assayed by flow cytometry. (D) AIF nuclear translocation pattern of each group is displayed. a2p<0.01, a3p<0.005 vs. 0 μM of treatment; b3p<0.005 vs. 10 μM regorafenib; c1p<0.05, c2p<0.01, c3p<0.005 vs. 15 μM cisplatin scale bar = 50 μM.

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    Figure 3.

    Suppression of metastasis effect was found in regorafenib combined with cisplatin in A549 cells. A549 cells were treated with 10 μM regorafenib, 15 μM cisplatin and their combination for 48 h. (A) Migration and invasion pattern of A549 after different treatments are displayed. The quantification of (B) migration area and (C) invasion area after different treatments are presented. (D) The metastasis related proteins expression pattern and quantification bar chart are displayed. a2p<0.01, a3p<0.005 vs. 0 μM of treatment; b2p<0.01, b3p<0.005 vs. 10 μM regorafenib; c2p<0.01 vs. 15 μM cisplatin scale bar = 100 μM.

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Induction of Apoptosis and Inhibition of EGFR/NF-κB Signaling Are Associated With Regorafenib-sensitized Non-small Cell Lung Cancer to Cisplatin
JENG-YUAN WU, YUEH-SHAN WENG, YI-CHOU CHIOU, FEI-TING HSU, I-TSANG CHIANG
In Vivo Sep 2021, 35 (5) 2569-2576; DOI: 10.21873/invivo.12539

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Induction of Apoptosis and Inhibition of EGFR/NF-κB Signaling Are Associated With Regorafenib-sensitized Non-small Cell Lung Cancer to Cisplatin
JENG-YUAN WU, YUEH-SHAN WENG, YI-CHOU CHIOU, FEI-TING HSU, I-TSANG CHIANG
In Vivo Sep 2021, 35 (5) 2569-2576; DOI: 10.21873/invivo.12539
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Keywords

  • Regorafenib
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  • Non-small cell lung cancer
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