Preclinical Study of Novel Curcumin Analogue SSC-5 Using Orthotopic Tumor Xenograft Model for Esophageal Squamous Cell Carcinoma.
- Author:
Lai Nar TUNG
1
;
Senchuan SONG
;
Kin Tak CHAN
;
Mei Yuk CHOI
;
Ho Yu LAM
;
Chung Man CHAN
;
Zhiyong CHEN
;
Hector K. WANG
;
Hoi Ting LEUNG
;
Simon LAW
;
Yanmin HUANG
;
Huacan SONG
;
Nikki P. LEE
Author Information
- Publication Type:Original Article
- Keywords: Curcumin; Esophageal squamous cell carcinoma
- MeSH: Animals; Apoptosis; Body Weight; Carcinogenesis; Carcinoma, Squamous Cell*; Cell Cycle Checkpoints; Cell Proliferation; Curcumin*; Epithelial Cells*; Esophageal Stenosis; Esophagus; Heterografts*; Mass Screening; Mice; Mice, Nude; Therapeutic Uses
- From:Cancer Research and Treatment 2018;50(4):1362-1377
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Tumor xenograft model is an indispensable animal cancer model. In esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft model establishes tumor xenograft in the animal esophagus, which allows the study of tumorigenesis in its native microenvironment. MATERIALS AND METHODS: In this study,we described two simple and reproducible methods to develop tumor xenograft at the cervical or the abdominal esophagus in nude mice by direct injection of ESCC cells in the esophageal wall. RESULTS: In comparing these two methods, the cervical one presented with more clinically relevant features, i.e., esophageal stricture, body weight loss and poor survival. In addition, the derived tumor xenografts accompanied a rapid growth rate and a high tendency to invade into the surrounding structures. This model was subsequently used to study the anti-tumor effect of curcumin, which is known for its potential therapeutic effects in various diseases including cancers, and its analogue SSC-5. SSC-5 was selected among the eight newly synthesized curcumin analogues based on its superior anti-tumor effect demonstrated in an MTT cell proliferation assay and its effects on apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor growth and invasion. CONCLUSION: Taken together, we have established a clinically relevant orthotopic tumor xenograft model that can serve as a preclinical tool for screening new anti-tumor compounds, e.g., SSC-5, in ESCC.
