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.
Int J Oncol. 2017 Aug;51(2):695-701. doi: 10.3892/ijo.2017.4056. Epub 2017 Jun 26.
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.
本研究旨在评估经肝动脉注入二氧化碳(CO2)饱和溶液对顺铂在兔 VX2 肝癌模型中抗肿瘤作用的增敏效果。将 40 只荷 VX2 肝癌的日本大白兔随机分为四组,分别经肝固有动脉注入生理盐水(对照组)、CO2 饱和溶液(CO2 组)、顺铂溶液(顺铂组)和 CO2 饱和溶液和顺铂溶液(联合组)。采用增强 CT 计算肿瘤体积(TV)和相对肿瘤体积(RTV),RTV=(第 3 天或第 7 天的 TV)/(第 0 天的 TV)×100。缺氧诱导因子-1α(HIF-1α)和碳酸酐酶 IX(CA IX)染色用于评估细胞缺氧情况。分析Cleaved caspase-3 和 Cleaved caspase-9 以评估肿瘤细胞凋亡。对照组第 3 天和第 7 天的平均 RTV 分别为 202.6±23.7%和 429.2±94.8%;CO2 组分别为 172.2±38.1%和 376.5±61.1%;顺铂组分别为 156.1±15.1%和 269.6±45.2%;联合组分别为 118.3±28.1%和 210.3±55.1%。CO2 组的 RTV 明显低于对照组(第 3 天,P<0.05),联合组的 RTV 明显低于顺铂组(第 3 天和第 7 天,P<0.05)。CO2 组和联合组的 HIF-1α 和 CA IX 抑制以及 Cleaved caspase-3 和 Cleaved caspase-9 的表达增加均高于其他两组。经肝动脉注入 CO2 饱和溶液可抑制兔 VX2 肝癌生长并增强顺铂的抗肿瘤作用。