Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time

PL Dai,1,2,* XS Du,3,* Y Hou,1,* L Li,1 YX Xia,1 L Wang,1 HX Chen,1 L Chang,1 WH Li1 1Radiotherapy Department, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650100, People’s Republic of China; 2Kunming Medical University, Kunming, Yunnan 650100, People&rs...

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Main Authors: Dai PL, Du XS, Hou Y, Li L, Xia YX, Wang L, Chen HX, Chang L, Li WH
Format: Article
Language:English
Published: Dove Medical Press 2020-04-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/different-proteins-regulated-apoptosis-proliferation-and-metastasis-of-peer-reviewed-article-CMAR
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author Dai PL
Du XS
Hou Y
Li L
Xia YX
Wang L
Chen HX
Chang L
Li WH
author_facet Dai PL
Du XS
Hou Y
Li L
Xia YX
Wang L
Chen HX
Chang L
Li WH
author_sort Dai PL
collection DOAJ
description PL Dai,1,2,* XS Du,3,* Y Hou,1,* L Li,1 YX Xia,1 L Wang,1 HX Chen,1 L Chang,1 WH Li1 1Radiotherapy Department, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650100, People’s Republic of China; 2Kunming Medical University, Kunming, Yunnan 650100, People’s Republic of China; 3Oncology Department, The Fifth People’s Hospital of Huaian, Jiangsu 223001, People’s Republic of China*These authors contributed equally to this workCorrespondence: L Chang; WH Li Email changli1981@126.com; wenhuili64@aliyun.comIntroduction: The biological changes after irradiation in lung cancer cells are important to reduce recurrence and metastasis of lung cancer. To optimize radiotherapy of lung adenocarcinoma, our study systematically explored the mechanisms of biological behaviors in residual A549 and XWLC-05 cells after irradiation.Methods: Colony formation assay, cell proliferation assay, cell migration assay, flow cytometry, BALB/C-nu mice xenograft models and Western blot of pan-AKT, p-Akt380, p-Akt473, PCNA, DNA-PKCS, KU70, KU80, CD133, CD144, MMP2 and P53 were used in our study to assess biological changes after irradiation with 0, 4 and 8 Gy at 0– 336 hr after irradiation in vitro and 20 Gy at transplantation group, irradiated transplantation group, residual tumor 0, 7, 14, 21, and 28 days groups in vivo.Results: The ability of cell proliferation and radiosensitivity of residual XWLC-05 cells was better than A549 cells after radiation in vivo and in vitro. MMP-2 has statistical differences in vitro and in vivo and increased with the migratory ability of cells in vitro. PCNA and P53 have statistical differences in XWLC-05 and A549 cells and the changes of them are similar to the proliferation of residual cells within first 336 hr after irradiation in vitro. Pan-AKT increased after irradiation, and residual tumor 21-day group (1.5722) has statistic differences between transplantation group (0.9763, p=0.018) and irradiated transplantation group (0.8455, p=0.006) in vivo. Pan-AKT rose to highest when 21-day after residual tumor reach to 0.5 mm2. MMP2 has statistical differences between transplantation group (0.4619) and residual tumor 14-day group (0.8729, p=0.043). P53 has statistical differences between residual tumor 7-day group (0.6184) and residual tumor 28 days group (1.0394, p=0.007). DNA-PKCS has statistical differences between residual tumor 28 days group (1.1769) and transplantation group (0.2483, p=0.010), irradiated transplantation group (0.1983, p=0.002) and residual tumor 21 days group (0.2017, p=0.003), residual tumor 0 days group (0.5992) and irradiated transplantation group (0.1983, p=0.027) and residual tumor 21 days group (0.2017, p=0.002). KU80 and KU70 have no statistical differences at any time point.Conclusion: Different proteins regulated apoptosis, proliferation and metastasis of lung adenocarcinoma after radiotherapy at different times. MMP-2 might regulate metastasis ability of XWLC-05 and A549 cells in vitro and in vivo. PCNA and P53 may play important roles in proliferation of vitro XWLC-05 and A549 cells within first 336 hr after irradiation in vitro. After that, P53 may through PI3K/AKT pathway regulate cell proliferation after irradiation in vitro. DNA-PKCS may play a more important role in DNA damage repair than KU70 and KU80 after 336 hr in vitro because it rapidly rose than KU70 and KU80 after irradiation. Different cells have different time rhythm in apoptosis, proliferation and metastasis after radiotherapy. Time rhythm of cells after irradiation should be delivered and more attention should be paid to resist cancer cell proliferation and metastasis.Keywords: lung adenocarcinoma, XWLC-05 cells, biological, radiation
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spelling doaj.art-cc8a97d828864ba0b0204669e77bf5cd2022-12-22T01:14:07ZengDove Medical PressCancer Management and Research1179-13222020-04-01Volume 122437244752899Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different TimeDai PLDu XSHou YLi LXia YXWang LChen HXChang LLi WHPL Dai,1,2,* XS Du,3,* Y Hou,1,* L Li,1 YX Xia,1 L Wang,1 HX Chen,1 L Chang,1 WH Li1 1Radiotherapy Department, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650100, People’s Republic of China; 2Kunming Medical University, Kunming, Yunnan 650100, People’s Republic of China; 3Oncology Department, The Fifth People’s Hospital of Huaian, Jiangsu 223001, People’s Republic of China*These authors contributed equally to this workCorrespondence: L Chang; WH Li Email changli1981@126.com; wenhuili64@aliyun.comIntroduction: The biological changes after irradiation in lung cancer cells are important to reduce recurrence and metastasis of lung cancer. To optimize radiotherapy of lung adenocarcinoma, our study systematically explored the mechanisms of biological behaviors in residual A549 and XWLC-05 cells after irradiation.Methods: Colony formation assay, cell proliferation assay, cell migration assay, flow cytometry, BALB/C-nu mice xenograft models and Western blot of pan-AKT, p-Akt380, p-Akt473, PCNA, DNA-PKCS, KU70, KU80, CD133, CD144, MMP2 and P53 were used in our study to assess biological changes after irradiation with 0, 4 and 8 Gy at 0– 336 hr after irradiation in vitro and 20 Gy at transplantation group, irradiated transplantation group, residual tumor 0, 7, 14, 21, and 28 days groups in vivo.Results: The ability of cell proliferation and radiosensitivity of residual XWLC-05 cells was better than A549 cells after radiation in vivo and in vitro. MMP-2 has statistical differences in vitro and in vivo and increased with the migratory ability of cells in vitro. PCNA and P53 have statistical differences in XWLC-05 and A549 cells and the changes of them are similar to the proliferation of residual cells within first 336 hr after irradiation in vitro. Pan-AKT increased after irradiation, and residual tumor 21-day group (1.5722) has statistic differences between transplantation group (0.9763, p=0.018) and irradiated transplantation group (0.8455, p=0.006) in vivo. Pan-AKT rose to highest when 21-day after residual tumor reach to 0.5 mm2. MMP2 has statistical differences between transplantation group (0.4619) and residual tumor 14-day group (0.8729, p=0.043). P53 has statistical differences between residual tumor 7-day group (0.6184) and residual tumor 28 days group (1.0394, p=0.007). DNA-PKCS has statistical differences between residual tumor 28 days group (1.1769) and transplantation group (0.2483, p=0.010), irradiated transplantation group (0.1983, p=0.002) and residual tumor 21 days group (0.2017, p=0.003), residual tumor 0 days group (0.5992) and irradiated transplantation group (0.1983, p=0.027) and residual tumor 21 days group (0.2017, p=0.002). KU80 and KU70 have no statistical differences at any time point.Conclusion: Different proteins regulated apoptosis, proliferation and metastasis of lung adenocarcinoma after radiotherapy at different times. MMP-2 might regulate metastasis ability of XWLC-05 and A549 cells in vitro and in vivo. PCNA and P53 may play important roles in proliferation of vitro XWLC-05 and A549 cells within first 336 hr after irradiation in vitro. After that, P53 may through PI3K/AKT pathway regulate cell proliferation after irradiation in vitro. DNA-PKCS may play a more important role in DNA damage repair than KU70 and KU80 after 336 hr in vitro because it rapidly rose than KU70 and KU80 after irradiation. Different cells have different time rhythm in apoptosis, proliferation and metastasis after radiotherapy. Time rhythm of cells after irradiation should be delivered and more attention should be paid to resist cancer cell proliferation and metastasis.Keywords: lung adenocarcinoma, XWLC-05 cells, biological, radiationhttps://www.dovepress.com/different-proteins-regulated-apoptosis-proliferation-and-metastasis-of-peer-reviewed-article-CMARlung adenocarcinomaxwlc-05 cellsbiologicalradiation
spellingShingle Dai PL
Du XS
Hou Y
Li L
Xia YX
Wang L
Chen HX
Chang L
Li WH
Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time
Cancer Management and Research
lung adenocarcinoma
xwlc-05 cells
biological
radiation
title Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time
title_full Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time
title_fullStr Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time
title_full_unstemmed Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time
title_short Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time
title_sort different proteins regulated apoptosis proliferation and metastasis of lung adenocarcinoma after radiotherapy at different time
topic lung adenocarcinoma
xwlc-05 cells
biological
radiation
url https://www.dovepress.com/different-proteins-regulated-apoptosis-proliferation-and-metastasis-of-peer-reviewed-article-CMAR
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