Cancer Research and Treatment

Original Articles

Preclinical Study of Novel Curcumin Analogue SSC-5 Using Orthotopic Tumor Xenograft Model for Esophageal Squamous Cell Carcinoma: Lai Nar Tung, 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; Cancer Res Treat. 2018;50(4):1362-1377. Published online January 24, 2018; DOI: https://doi.org/10.4143/crt.2017.353

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.

Citations

Citations to this article as recorded by

GE11‐Modified Red Blood Cell Membrane Nanoprodrug for ROS‐Responsive Synergistic Photothermal–Chemotherapy of Esophageal Cancer
Yang Chen, Li Zhu, Wei Xu, Qi Chen, Fei Teng, Kaiwen Bao, Lu Zhang, Yuan Wang, Wei Wu, Zhiqiang Wang
Advanced Healthcare Materials.2026;[Epub] CrossRef
Unveiling Another Dimension: Advanced Visualization of Cancer Invasion and Metastasis via Micro-CT Imaging
Sergey Tkachev, Vladimir Brosalov, Oleg Kit, Alexey Maksimov, Anna Goncharova, Evgeniy Sadyrin, Alexandra Dalina, Elena Popova, Anton Osipenko, Mark Voloshin, Nikolay Karnaukhov, Peter Timashev
Cancers.2025; 17(7): 1139. CrossRef
Network pharmacology and molecular docking reveal the mechanisms of curcumin activity against esophageal squamous cell carcinoma
Jian Wang, Zhilong Zhang, Qian Li, Zilong Hu, Yuan Chen, Hao Chen, Wei Cai, Qiancheng Du, Peng Zhang, Dian Xiong, Shugao Ye
Frontiers in Pharmacology.2024;[Epub] CrossRef
Curcumin: recent updates on gastrointestinal cancers
Muhammad Imran, Farhan Saeed, Suliman A. Alsagaby, Ali Imran, Ishtiaque Ahmad, Ahmad H. El Ghorab, Mohamed A. Abdelgawad, Tahira Batool Qaisrani, Tahir Mehmood, Maryam Umar, Muhammad Arslan Mumtaz, Arfaa Sajid, Qaisar Manzoor, Muzzamal Hussain, Waleed Al
CyTA - Journal of Food.2023; 21(1): 502. CrossRef
The anticancer effects of curcumin and clinical research progress on its effects on esophageal cancer
Shimeng Wang, Xinliang Gao, Jialin Li, Shixiong Wei, Yifeng Shao, Yipeng Yin, Duo Zhang, Mingbo Tang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Therapeutic effect of curcumin in gastrointestinal cancers: A comprehensive review
Korosh Morshedi, Sarina Borran, Mohammad Saeid Ebrahimi, Mohammad Jaber Masoud khooy, Zeynab Sadat Seyedi, Atefeh Amiri, Mohammad Abbasi‐Kolli, Maryam Fallah, Haroon Khan, Amirhossein Sahebkar, Hamed Mirzaei
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Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
Shoh Yajima, Kotaro Sugawara, Miwako Iwai, Minoru Tanaka, Yasuyuki Seto, Tomoki Todo
Molecular Therapy Oncolytics.2021; 23: 402. CrossRef
Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status
AmirReza Hesari, Mitra Azizian, Alireza Sheikhi, Abolfazl Nesaei, Shahin Sanaei, Nazanin Mahinparvar, Maryam Derakhshani, Pegah Hedayt, Faezeh Ghasemi, Hamed Mirzaei
International Journal of Cancer.2019; 144(6): 1215. CrossRef
Latest in Vitro and in Vivo Assay, Clinical Trials and Patents in Cancer Treatment using Curcumin: A Literature Review
Kevin Doello, Raúl Ortiz, Pablo J. Alvarez, Consolación Melguizo, Laura Cabeza, José Prados
Nutrition and Cancer.2018; 70(4): 569. CrossRef
Tumor xenograft animal models for esophageal squamous cell carcinoma
Nikki P. Lee, Chung Man Chan, Lai Nar Tung, Hector K. Wang, Simon Law
Journal of Biomedical Science.2018;[Epub] CrossRef

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Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE₂: Ivan Ho Yuen Pun, Dessy Chan, Sau Hing Chan, Po Yee Chung, Yuan Yuan Zhou, Simon Law, Alfred King Yin Lam, Chung Hin Chui, Albert Sun Chi Chan, Kim Hung Lam, Johnny Cheuk On Tang; Cancer Res Treat. 2017;49(1):219-229. Published online July 18, 2016; DOI: https://doi.org/10.4143/crt.2016.190

Abstract PDF Supplementary Material PubReader ePub

Purpose
83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis.
Materials and Methods
A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E2 (PGE2) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450.
Results
83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft.
Conclusion
The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.

Citations

Citations to this article as recorded by

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International Journal of Molecular Medicine.2024;[Epub] CrossRef
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Cancer Prevention Research.2022; 15(6): 355. CrossRef
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Bioorganic Chemistry.2020; 96: 103592. CrossRef
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