Effect of the chemoprotectant tempol on anti-tumor activity of cisplatin.
10.12122/j.issn.1673-4254.2019.08.02
- Author:
Shuangyan YE
1
;
Sisi ZENG
1
;
Mengqiu HUANG
1
;
Jianping CHEN
1
;
Xi CHEN
1
;
Pengfei XU
1
;
Qianli WANG
1
;
Wenwen GAO
1
;
Bingsheng YANG
2
;
Bingtao HAO
1
;
Wenhuan HUANG
3
;
Qiuzhen LIU
1
Author Information
1. Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University/Guangdong Provincial Key Laboratory of Cancer Immunotherapy/Guangzhou Key Laboratory of Tumor Immunology Research, Guangzhou 510515, China.
2. Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
3. National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
- Publication Type:Journal Article
- Keywords:
anti-oxidants;
chemotherapy;
cisplatin;
drug toxicity;
reactive oxygen species;
tempol
- MeSH:
Animals;
Antineoplastic Agents;
Antioxidants;
Apoptosis;
Cell Line, Tumor;
Cell Proliferation;
Cisplatin;
Cyclic N-Oxides;
pharmacology;
Drug Resistance, Neoplasm;
Humans;
Mice;
Spin Labels
- From:
Journal of Southern Medical University
2019;39(8):883-890
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of the chemoprotectant tempol on the anti-tumor activity of cisplatin (DDP).
METHODS:The cellular toxicity of tempol in human colon cancer SW480 cells and mouse colon cancer CT26 cells were evaluated using MTT and cell counting kit-8 assays. CalcuSyn software analysis was used to determine the interaction between tempol and DDP in inhibition of the cell viability. A subcutaneous homograft mouse model of colon cancer was established. The mice were randomly divided into control group, tempol group, cisplatin group and tempol + DDP treatment group with intraperitoneal injections of the indicated agents. The tumor size, body weight and lifespan of the mice were measured, and HE staining was used to analyze the cytotoxic effect of the agents on the kidney and liver. Immunohistochemistry and Western blotting were performed to detect the expression of Bax and Bcl2 in the tumor tissue, and TUNEL staining was used to analyze the tumor cell apoptosis. The level of reactive oxygen species (ROS) in the tumor tissue was determined using flow cytometry.
RESULTS:Tempol showed inhibitory effects on the viability of SW480 and CT26 cells. CalcuSyn software analysis showed that tempol had a synergistic anti-tumor effect with DDP (CI < 1). In the homograft mouse model, tempol treatment alone did not produce obvious anti-tumor effect. HE staining showed that the combined use of tempol and DDP alleviated DDP-induced fibrogenesis in the kidneys, but tempol also reduced the anti-tumor activity of DDP. Compared with the mice treated with DDP alone, the mice treated with both tempol and DDP had a significantly larger tumor size ( < 0.01) and a shorter lifespan ( < 0.05). Tempol significantly reversed DDP-induced expression of Bax and Bcl2 in the tumor tissue and tumor cell apoptosis ( < 0.001), and obviously reduced the elevation of ROS level in the tumor tissue induced by DDP treatment ( < 0.05).
CONCLUSIONS:Tempol can attenuate the anti-tumor effect of DDP while reducing the side effects of DDP. Caution must be taken and the risks and benefits should be carefully weighed when considering the use of tempol as an anti-oxidant to reduce the toxicities of DDP.
