TLR4 siRNA inhibits proliferation and invasion in colorectal cancer cells by downregulating ACAT1 expression.

AIMS

Toll-like receptor 4 (TLR4) is involved in tumor development. Numerous studies have confirmed that TLR4 mediates processes in tumorigenesis, for example, inflammation, proliferation and invasion. However, the effects of TLR4 on colorectal cancer development have not been fully elucidated. The present study aimed to evaluate the effects and mechanisms of TLR4 on colorectal cancer development.

MAIN METHODS

The expression of TLR4 and Acyl coenzyme A cholesterol acyltransferase 1 (ACAT1) in colorectal cancer tissues and cell lines was detected using RT-PCR and Western blot. The nude mouse xenograft model was established by subcutaneous injection of SW480 cells transfected with TLR4 scramble or TLR4 siRNA. CCK8 and transwell assays were used to evaluate the effects of TLR4 silencing on cell proliferation, migration and invasion in HT29 and SW480. RT-PCR and Western blot was used to determine the regulation between TLR4 and ACAT1.

KEY FINDINGS

Both TLR4 and ACAT1 were highly expressed in colorectal cancer tissues and cell lines. Inhibition of TLR4 reduced tumor growth, suppressed cell proliferation, migration and invasion in HT29 and SW480. TLR4 siRNA decreased ACAT1 expression in HT29, and that overexpression of ACAT1 by pLV-Neo-ACAT1 abolished the effects of TLR4 on colorectal cancer cell lines.

SIGNIFICANCE

TLR4 siRNA inhibits cell proliferation, migration and invasion by suppressing ACAT1 expression, suggesting that TLR4 may be a potential therapeutic target for the treatment of colorectal cancer.