Abstract

Objectives Intensive efforts have been made in the area of identifying drug resistance modulators from traditional Chinese medicine . Various natural plant extracts have been reported for their reversal effect of drug resistance in cancers . This study was to assess the reversal potential of Curcumae longae Rhizoma extract (CLRE) in 5-Fluorouracil (5-Fu) resistance to colon cancer and explore its underly mechanism. Methods Increased concentrations of 5-Fu were used to culture SW480. A series of concentrations of CLRE were used to treat the 5-Fu resistant SW480 cells. WST-8 assay was used to detect the cell viability . Cell apoptosis was assessed by SuperView™ 488 Caspase-3 Assay Kit. The quantification of mentioned factors was archived by RT-qPCR. Network pharmacology analysis was used to explore the target of CLRE. Results 5-Fu resistant cell line (SW480/5-FuR) was established. The IC50 value of CLRE against SW480/5-FuR was 181.0 ± 14.12 µg/ml. CLRE can resensitize the SW480/5-FuR to 5-Fu by inhibiting cell growth. The combination treatment (CLRE+5-Fu) induced cell apoptosis via inhibition of bcl-2 and activation of caspase-3 and bax. Three active ingredients from CLRE were identified. TLR4 was targeted by these three ingredients and linked these ingredients to PI3K/Akt/mTOR pathway. The levels of TLR4, PI3K, AKT1, and mTORC1 mRNA were decreased when 5-Fu was combined with CLRE. Conclusions CLRE could reverse 5-Fu resistance in colon cancer by inactivating TLR4/PI3K/AKT/mTORC1 pathway. This finding might provide a molecular basis and a valuable direction for further clinical applications and research for treating 5-Fu resistant colon cancer.