Intra-arterially infused carbon dioxide-saturated solution for sensitizing the anticancer effect of cisplatin in a rabbit VX2 liver tumor model

Katayama,Naoto; Sugimoto,Koji; Okada,Takuya; Ueha,Takeshi; Sakai,Yoshitada; Akiyoshi,Hideo; Mie,Keiichiro; Ueshima,Eisuke; Sofue,Keitaro; Koide,Yutaka; Tani,Ryuichiro; Gentsu,Tomoyuki; Yamaguchi,Masato

doi:10.3892/ijo.2017.4056

Intra-arterially infused carbon dioxide-saturated solution for sensitizing the anticancer effect of cisplatin in a rabbit VX2 liver tumor model

Authors:
- Naoto Katayama
- Koji Sugimoto
- Takuya Okada
- Takeshi Ueha
- Yoshitada Sakai
- Hideo Akiyoshi
- Keiichiro Mie
- Eisuke Ueshima
- Keitaro Sofue
- Yutaka Koide
- Ryuichiro Tani
- Tomoyuki Gentsu
- Masato Yamaguchi
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Affiliations: Department of Radiology and Center for Endovascular Therapy, Kobe University Hospital, Chuo-ku, Kobe 650-0017, Japan, Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan, Laboratory of Veterinary Surgery, Department of Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan
Published online on: June 26, 2017 https://doi.org/10.3892/ijo.2017.4056
Pages: 695-701

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Abstract

The present study aimed to evaluate the efficacy of an intra-arterially infused carbon dioxide (CO2)-saturated solution in sensitizing the anticancer effect of cisplatin in a rabbit VX2 liver tumor model. Forty VX2 liver tumor-bearing Japanese white rabbits were randomly divided into four groups and infused via the proper hepatic artery with a saline solution (control group), CO2-saturated solution (CO2 group), cisplatin solution (cisplatin group), or CO2-saturated solution and cisplatin solution (combined group). The tumor volume (TV) and the relative tumor volume (RTV), RTV = (TV on day 3 or 7)/(TV on day 0) x 100, were calculated using contrast-enhanced computed tomography. Hypoxia-inducible factor-1α (HIF‑1α) and carbonic anhydrase IX (CA IX) staining were used to evaluate cellular hypoxia. Cleaved caspase-3 and cleaved caspase-9 were analyzed to assess tumor apoptosis. The mean RTV on days 3 and 7 were 202.6±23.7 and 429.2±94.8%, respectively, in the control group; 172.2±38.1 and 376.5±61.1% in the CO2 group; 156.1±15.1 and 269.6±45.2% in the cisplatin group; and 118.3±28.1 and 210.3±55.1% in the combined group. RTV was significantly lower in the CO2 group than in the control group (day 3; P<0.05), and in the combined group than in the cisplatin group (days 3 and 7; P<0.05). HIF-1α and CA IX suppression, and increased cleaved caspase-3 and cleaved caspase-9 expression, were detected in the CO2 and combined groups, compared with the other two groups. An intra-arterially infused CO2-saturated solution inhibits liver VX2 tumor growth and sensitizes the anticancer effect of cisplatin.

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