Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer

Abstract Although the concurrent use of a chemotherapeutic agent and radiotherapy improves survival in patients with locally advanced or recurrent cervical cancer, severe side effects related to chemotherapy are frequent and may result in a low quality of life for the patients. In this study, we inv...

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Autores principales:	Yoo-Young Lee, Young-Jae Cho, Sung-won Shin, Changhoon Choi, Ji-Yoon Ryu, Hye-Kyung Jeon, Jung-Joo Choi, Jae Ryoung Hwang, Chel Hun Choi, Tae-Joong Kim, Byoung- Gie Kim, Duk-Soo Bae, Won Park, Jeong-Won Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37fc5faa39024327940cb72635355416
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spelling	oai:doaj.org-article:37fc5faa39024327940cb726353554162021-12-02T15:09:54ZAnti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer10.1038/s41598-019-51959-32045-2322https://doaj.org/article/37fc5faa39024327940cb726353554162019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51959-3https://doaj.org/toc/2045-2322Abstract Although the concurrent use of a chemotherapeutic agent and radiotherapy improves survival in patients with locally advanced or recurrent cervical cancer, severe side effects related to chemotherapy are frequent and may result in a low quality of life for the patients. In this study, we investigated the effects of a combination of Wee1 inhibitor (AZD1775) and irradiation in cervical cancer. In vitro effects of AZD1775 with irradiation in human cervical cancer cells were assessed by clonogenic survival and apoptosis assays. The effects on DNA damage response signaling and the cell cycle were also explored. Tumor growth delay was evaluated to investigate the in vivo effects of AZD1775 with irradiation in cervical cancer mouse models, including xenografts and patient-derived xenografts (PDXs). The co-treatment of AZD1775 and irradiation significantly decreased clonogenic survival and increased apoptosis in cervical cancer cells. These effects were associated with G2 checkpoint abrogation which resulted in persistent DNA damage. Both in the xenografts and the PDXs, the co-treatment significantly decreased tumor growth compared tothe irradiation alone (p < 0.05). These results demonstrate that the Wee1 inhibitor (AZD1775) can be considered as a potential alternative as a radiosensitizer in cervical cancer instead of a chemotherapeutic agent such as cisplatin.Yoo-Young LeeYoung-Jae ChoSung-won ShinChanghoon ChoiJi-Yoon RyuHye-Kyung JeonJung-Joo ChoiJae Ryoung HwangChel Hun ChoiTae-Joong KimByoung- Gie KimDuk-Soo BaeWon ParkJeong-Won LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoo-Young Lee Young-Jae Cho Sung-won Shin Changhoon Choi Ji-Yoon Ryu Hye-Kyung Jeon Jung-Joo Choi Jae Ryoung Hwang Chel Hun Choi Tae-Joong Kim Byoung- Gie Kim Duk-Soo Bae Won Park Jeong-Won Lee Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer
description	Abstract Although the concurrent use of a chemotherapeutic agent and radiotherapy improves survival in patients with locally advanced or recurrent cervical cancer, severe side effects related to chemotherapy are frequent and may result in a low quality of life for the patients. In this study, we investigated the effects of a combination of Wee1 inhibitor (AZD1775) and irradiation in cervical cancer. In vitro effects of AZD1775 with irradiation in human cervical cancer cells were assessed by clonogenic survival and apoptosis assays. The effects on DNA damage response signaling and the cell cycle were also explored. Tumor growth delay was evaluated to investigate the in vivo effects of AZD1775 with irradiation in cervical cancer mouse models, including xenografts and patient-derived xenografts (PDXs). The co-treatment of AZD1775 and irradiation significantly decreased clonogenic survival and increased apoptosis in cervical cancer cells. These effects were associated with G2 checkpoint abrogation which resulted in persistent DNA damage. Both in the xenografts and the PDXs, the co-treatment significantly decreased tumor growth compared tothe irradiation alone (p < 0.05). These results demonstrate that the Wee1 inhibitor (AZD1775) can be considered as a potential alternative as a radiosensitizer in cervical cancer instead of a chemotherapeutic agent such as cisplatin.
format	article
author	Yoo-Young Lee Young-Jae Cho Sung-won Shin Changhoon Choi Ji-Yoon Ryu Hye-Kyung Jeon Jung-Joo Choi Jae Ryoung Hwang Chel Hun Choi Tae-Joong Kim Byoung- Gie Kim Duk-Soo Bae Won Park Jeong-Won Lee
author_facet	Yoo-Young Lee Young-Jae Cho Sung-won Shin Changhoon Choi Ji-Yoon Ryu Hye-Kyung Jeon Jung-Joo Choi Jae Ryoung Hwang Chel Hun Choi Tae-Joong Kim Byoung- Gie Kim Duk-Soo Bae Won Park Jeong-Won Lee
author_sort	Yoo-Young Lee
title	Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer
title_short	Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer
title_full	Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer
title_fullStr	Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer
title_full_unstemmed	Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer
title_sort	anti-tumor effects of wee1 kinase inhibitor with radiotherapy in human cervical cancer
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/37fc5faa39024327940cb72635355416
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Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer

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