Diclofenac potentiates the antitumor effect of cisplatin in a xenograft mouse model transplanted with cisplatin-resistant cells without enhancing cisplatin-induced nephrotoxicity

Okamoto, Keisuke; Ueda, Hinata; Saito, Yoshitaka; Narumi, Katsuya; Furugen, Ayako; Kobayashi, Masaki

Diclofenac potentiates the antitumor effect of cisplatin in a xenograft mouse model transplanted with cisplatin-resistant cells without enhancing cisplatin-induced nephrotoxicity

Okamoto, Keisuke; Ueda, Hinata; Saito, Yoshitaka et al.

Drug metabolism and pharmacokinetics, 2021, 41, 100417

Permalink : https://hdl.handle.net/2115/88126

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アクセス権	open access
URI	https://hdl.handle.net/2115/88126
タイトル	Diclofenac potentiates the antitumor effect of cisplatin in a xenograft mouse model transplanted with cisplatin-resistant cells without enhancing cisplatin-induced nephrotoxicity
著者	Okamoto, Keisuke ; Ueda, Hinata ; Saito, Yoshitaka ; Narumi, Katsuya ; Furugen, Ayako ; Kobayashi, Masaki
著者名 Okamoto, Keisuke
著者名 Ueda, Hinata
e-Rad_Researcher 00835001 著者名 Saito, Yoshitaka
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
言語	英語
キーワード	Cisplatin
	Diclofenac
	Celecoxib
	Xenograft
	Nephrotoxicity
	Antitumor effect
発行日	2021-12
出版者	Japanese Society for the Study of Xenobiotics
	JSSX
	日本薬物動態学会
収録物名	Drug metabolism and pharmacokinetics
巻(号)	41
ページ	100417
抄録	Cisplatin (CDDP) is a well-known anticancer agent, and CDDP-induced nephrotoxicity (CIN) is one of the most serious adverse effects. Previously, we revealed that while celecoxib reduces CIN, diclofenac does not appear to enhance it. Furthermore, we reported that diclofenac additively enhances the cytotoxic effect of CDDP on CDDP-resistant A549 cells (A549/DDP cells) and their spheroids. In addition, celecoxib reduces the cytotoxic effect of CDDP on A549/DDP cells while demonstrating an anticancer effect; however, it enhanced the effect of CDDP cytotoxicity on spheroids. Therefore, we evaluated the effects of diclofenac or celecoxib on CIN and the antitumor effect of CDDP in a xenograft mouse model transplanted with A549/DDP cells. Although CDDP did not decrease tumor size and tumor weight, these parameters were significantly reduced following co-administration with diclofenac when compared with the control group. Conversely, celecoxib marginally suppressed the antitumor effect of CDDP. Moreover, CDDP increased the mRNA levels of kidney injury molecule 1 (Kim-1), a renal disorder marker, in the kidneys of xenograft mice; treatment with celecoxib and diclofenac did not impact Kim-1 mRNA levels increased by CDDP. In conclusion, diclofenac potentiated the antitumor effect of CDDP without enhancing CIN.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1347-4367
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.dmpk.2021.100417