Andrographis restrains the progression of colorectal cancer by inhibiting the KLF3/LEMD1 axis.

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.