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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Andrographis restrains the progression of colorectal cancer by inhibiting the KLF3/LEMD1 axis
Leyi Zhang1, Dongyang Li2, Yan Tang2
1Department of General Surgery, Chun'an First People's Hospital (Zhejiang Provincial People's Hospital Chun'an Branch), Hangzhou, China.
Abstract:
Andrographis has anti-cancer activity in various human cancers, including colorectal cancer. Our aim was to explore the detailed mechanisms underlying Andrographis in colorectal cancer progression. Andrographis inhibited the proliferation, reduced the invasive ability, and induced apoptosis in LoVo and HCT-116 cells. LEM domain containing 1 (LEMD1) expression was upregulated in colorectal cancer cells and tissue samples, and Andrographis significantly decreased LEMD1 expression in LoVo and HCT-116 cells. LEMD1 knockdown restrained colorectal cancer development by inhibiting proliferation and invasion and triggering apoptosis. Krüppel-like factor 3 (KLF3) targeted LEMD1 and positively regulated its expression in colorectal cancer cells. KLF3 overexpression reversed the anti-tumor effects of Andrographis on LoVo and HCT-116 cells, and this reversal was attenuated by LEMD1 silencing. Additionally, Andrographis hampered tumor growth and downregulated KLF3 and LEMD1 expression in colorectal cancer mice. In conclusion, Andrographis exerts anti-tumor activity in colorectal cancer through decreasing KLF3 and LEMD1 expression.
Insights
Andrographis shows anti-cancer effects in colorectal cancer by reducing LEM domain containing 1 (LEMD1) and Krüppel-like factor 3 (KLF3) expression, inhibiting tumor growth and spread.
Area of Science:
- Oncology
- Molecular Biology
- Natural Product Chemistry
Background:
- Andrographis possesses known anti-cancer properties, particularly against colorectal cancer.
- Understanding the precise molecular mechanisms of Andrographis in colorectal cancer is crucial for therapeutic development.
Purpose of the Study:
- To elucidate the detailed mechanisms by which Andrographis inhibits colorectal cancer progression.
- To investigate the roles of LEM domain containing 1 (LEMD1) and Krüppel-like factor 3 (KLF3) in Andrographis's anti-tumor effects.
Main Methods:
- Cell proliferation, invasion, and apoptosis assays were performed on colorectal cancer cell lines (LoVo and HCT-116).
- Gene expression analysis was conducted for LEMD1 and KLF3.
- In vivo studies utilized colorectal cancer mouse models to assess tumor growth and molecular changes.
Main Results:
- Andrographis significantly inhibited proliferation, invasion, and induced apoptosis in colorectal cancer cells.
- Andrographis downregulated the expression of LEM domain containing 1 (LEMD1) and Krüppel-like factor 3 (KLF3).
- LEMD1 knockdown mimicked Andrographis's anti-tumor effects, while KLF3 overexpression reversed them, indicating KLF3 targets LEMD1.
Conclusions:
- Andrographis exerts anti-cancer effects in colorectal cancer by suppressing the KLF3-LEMD1 signaling pathway.
- Targeting KLF3 and LEMD1 represents a potential therapeutic strategy for colorectal cancer treatment using Andrographis.
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