Kuroda Kohei, Yamashita Masamiti, Murahata Yusuke, Azuma Kazuo, Osaki Tomohiro, Tsuka Takeshi, Ito Norihiko, Imagawa Tomohiro, Okamoto Yoshiharu
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
Exp Ther Med. 2018 Sep;16(3):1597-1602. doi: 10.3892/etm.2018.6415. Epub 2018 Jul 6.
Tumor hypoxia is a severe problem affecting tumor therapy because it reduces the sensitivity of chemotherapy and radiation therapy. Ozone has been known to improve peripheral blood perfusion and oxygen partial pressure. The effect of ozonated water on tumor hypoxia, alone and in combination with an antitumor drug was studied in the present study. Following intraperitoneal administration of ozonated water to colon-26-bearing mice, the Hoechst 33342-positive area and the intratumoral oxygen partial pressure was significantly increased. The tumor growth rate was more suppressed when ozonated water was combined with cisplatin (CDDP) compared with CDDP treatment alone. The number of Ki-67-positive cells significantly decreased, whereas the number of TUNEL-positive cells significantly increased. The present study showed that ozonated water increased intratumoral blood perfusion and improved tumor hypoxia. In addition, ozonated water increased the therapeutic effect of CDDP. These findings, as well as previous reports, suggest that tumor growth is suppressed after treatment with ozonated water as the amount of CDDP reaching the tumor is increased when the intratumoral blood perfusion is increased due to the ozonated water. Thus, the administration of ozonated water may be a new therapeutic approach to solve current concerns regarding antitumor treatment.
肿瘤缺氧是影响肿瘤治疗的一个严重问题，因为它会降低化疗和放疗的敏感性。已知臭氧可改善外周血灌注和氧分压。本研究探讨了臭氧水单独及与抗肿瘤药物联合应用对肿瘤缺氧的影响。给荷瘤结肠-26小鼠腹腔注射臭氧水后，Hoechst 33342阳性面积和瘤内氧分压显著增加。与单独使用顺铂（CDDP）治疗相比，臭氧水与CDDP联合使用时肿瘤生长速率受到更明显的抑制。Ki-67阳性细胞数量显著减少，而TUNEL阳性细胞数量显著增加。本研究表明，臭氧水可增加瘤内血液灌注并改善肿瘤缺氧。此外，臭氧水可增强CDDP的治疗效果。这些发现以及之前的报道表明，由于臭氧水增加了瘤内血液灌注，使到达肿瘤的CDDP量增加，从而在用臭氧水处理后肿瘤生长受到抑制。因此，臭氧水给药可能是解决当前抗肿瘤治疗问题的一种新的治疗方法。
