Local Tumor Ischemia-Reperfusion Mediated By Ultrasound-Targeted Microbubble Destruction Enhances The Anti-Tumor Efficacy Of Doxorubicin Chemotherapy
Authors Wu M, Song Z, Zhang S, Dan Q, Tang C, Peng C, Liang Y, Zhang L, Wang H, Li Y
Received 1 August 2019
Accepted for publication 9 October 2019
Published 5 November 2019 Volume 2019:11 Pages 9387—9395
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Nakshatri
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 work
Correspondence: Yingjia Li
Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, No. 1023-1063, Sha Tai Nan Road, Baiyun District, Guangzhou 510515, People’s Republic of China
Tel +86 20 6164200
Department 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 China
Tel +86 755 22948200
Background: 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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]