Lambda-Carrageenan Enhances the Effects of Radiation Therapy in Cancer Treatment by Suppressing Cancer Cell Invasion and Metastasis through Racgap1 Inhibition

Wu, Ping-Hsiu; Onodera, Yasuhito; Recuenco, Frances C.; Giaccia, Amato J.; Le, Quynh-Thu; Shimizu, Shinichi; Shirato, Hiroki; Nam, Jin-Min

Lambda-Carrageenan Enhances the Effects of Radiation Therapy in Cancer Treatment by Suppressing Cancer Cell Invasion and Metastasis through Racgap1 Inhibition

Wu, Ping-Hsiu; Onodera, Yasuhito; Recuenco, Frances C. et al.

Cancers, 2019, 11(8), 1192

Permalink : https://hdl.handle.net/2115/76173

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/76173
タイトル	Lambda-Carrageenan Enhances the Effects of Radiation Therapy in Cancer Treatment by Suppressing Cancer Cell Invasion and Metastasis through Racgap1 Inhibition
著者	Wu, Ping-Hsiu ; Onodera, Yasuhito ; Recuenco, Frances C. ; Giaccia, Amato J. ; Le, Quynh-Thu ; Shimizu, Shinichi ; Shirato, Hiroki ; Nam, Jin-Min
著者名 Wu, Ping-Hsiu
e-Rad_Researcher 90435561 著者名 Onodera, Yasuhito
著者名 Recuenco, Frances C.
著者名 Giaccia, Amato J.
著者名 Le, Quynh-Thu
e-Rad_Researcher 50463724 著者名 Shimizu, Shinichi
e-Rad_Researcher 20187537 著者名 Shirato, Hiroki
e-Rad_Researcher 60414132 著者名 Nam, Jin-Min
言語	英語
キーワード	Carrageenan
	Invasion
	Metastasis
	RacGAP1
	Radiotherapy
発行日	2019-08
出版者	MDPI
収録物名	Cancers
巻(号)	11(8)
ページ	1192
抄録	Radiotherapy is used extensively in cancer treatment, but radioresistance and the metastatic potential of cancer cells that survive radiation remain critical issues. There is a need for novel treatments to improve radiotherapy. Here, we evaluated the therapeutic benefit of lambda-carrageenan (CGN) to enhance the efficacy of radiation treatment and investigated the underlying molecular mechanism. CGN treatment decreased viability in irradiated cancer cells and enhanced reactive oxygen species accumulation, apoptosis, and polyploid formation. Additionally, CGN suppressed radiation-induced chemoinvasion and invasive growth in 3D 1rECM culture. We also screened target molecules using a gene expression microarray analysis and focused on Rac GTPase-activating protein 1 (RacGAP1). Protein expression of RacGAP1 was upregulated in several cancer cell lines after radiation, which was significantly suppressed by CGN treatment. Knockdown of RacGAP1 decreased cell viability and invasiveness after radiation. Overexpression of RacGAP1 partially rescued CGN cytotoxicity. In a mouse xenograft model, local irradiation followed by CGN treatment significantly decreased tumor growth and lung metastasis compared to either treatment alone. Taken together, these results suggest that CGN may enhance the effectiveness of radiation in cancer therapy by decreasing cancer cell viability and suppressing both radiation-induced invasive activity and distal metastasis through downregulating RacGAP1 expression.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
EISSN	2072-6694
関連情報	PMID 31426369
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3390/cancers11081192