Cancer Management and Research (Nov 2019)
Local Tumor Ischemia-Reperfusion Mediated By Ultrasound-Targeted Microbubble Destruction Enhances The Anti-Tumor Efficacy Of Doxorubicin Chemotherapy
Abstract
Manxiang Wu,1,* Zhuqing Song,2,* Shiyu Zhang,1 Qing Dan,1 Caiyun Tang,3 Chao Peng,1 Yu Liang,1 Li Zhang,1 Hao Wang,4 Yingjia Li1 1Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 3Pharmaceutical Analysis Department, College of Pharmacy, Jiamusi University, Jiamusi, People’s Republic of China; 4Department of Neurosurgery, Shenzhen People‘s Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingjia LiDepartment of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, No. 1023-1063, Sha Tai Nan Road, Baiyun District, Guangzhou 510515, People’s Republic of ChinaTel +86 20 6164200Email [email protected] WangDepartment of Neurosurgery, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, No.1017 Dongmen North Road, Luohu District, Shenzhen 518020, People’s Republic of ChinaTel +86 755 22948200Email [email protected]: Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising noninvasive technique to change the tumor circulation, thus providing a potential method to increase reactive oxygen species (ROS) levels in tumors by inducing tumor tissue ischemia-reperfusion (IR). In this study, we investigated the feasibility of local tumor IR through UTMD to enhance the anti-tumor efficacy of doxorubicin (DOX) chemotherapy.Methods: UTMD was used to induce local tumor IR. After the major blood supply of the tumor was restored, DOX was intravenously injected into the tumor-bearing mice. The superoxide dismutase (SOD) and catalase (CAT) activity and ROS levels were examined, and the anti-tumor efficacy was evaluated.Results: UTMD blocked the circulation to the tumor for 30 mins. Slow reperfusion began to occur after 30 mins, and major blood supply was restored after 1 hr. The blood perfusion of the tumor completely recovered at 2 hrs. The activity of SOD in the tumors was significantly decreased at 2 hrs and 1 day after IR treatment with or without DOX treatment. The CAT activity showed no obvious changes at 2 hrs after IR treatment, whereas a significant decrease was found after 1 day in both the IR and DOX/IR groups. Moreover, higher levels of ROS were produced in the IR group and IR/DOX group. In vivo anti-tumor study indicated that the local tumor IR strategy may significantly enhance the anti-tumor efficacy of DOX chemotherapy.Conclusion: UTMD provides a novel, simple and non-invasive technique for tumor IR. In combination with chemotherapy, UTMD may have high great potential to improve the anti-tumor efficacy of chemotherapeutic drugs.Keywords: ischemia-reperfusion, ultrasound targeted microbubble destruction, breast tumor, doxorubicin, combined treatment
