Ursolic acid induces apoptosis and autophagy of HCT-8/5-FU cells

Abstract

[Abstract]: Objective: To observe the effects of ursolic acid (UA) on the apoptosis, autophagy and mTOR of human colorectal cancer (CRC) cells resistant to 5-FU (HCT-8/5-FU), and explore the mechanisms of UA reversing the multidrug resistance (MDR) of CRC. Methods: HCT-8 cells and its resistant cells to 5-FU (HCT-8/5-FU) were cultured to calculate the resistant index and confirmed the resistance of HCT-8/5-FU. The MTT assays were used to screen the suitable concentrations and the reversal fold of UA. The efflux function, proliferation, apoptosis, autophagy and their correlated proteins were determined through Doxorubucin staining, Rhodamine 123 staining, colony formation, Annexin V-PI double staining, Cyto-ID staining and Western blot after the HCT-8/5-FU were intervened with UA for 48 h. Results: HCT-8/5-FU cells are resistant to different chemotherapeutics, UA could reverse the MDR effectively. Furtherly, UA down-regulates the expression of ABCB1, ABCG2, p62, up-regulates Bax/Bcl-2 and LC3II/LC3I to inhibit the drug-efflux (P<0.05) and induce the apoptosis (P<0.05) and autophagy (P<0.05) via inhibiting the phosphorylation of mTOR. Conclusion: UA induces the apoptosis and autophagy, blocks the proliferation of HCT-8/5-FU cells via inhibiting the phosphoralation of mTOR, that maybe the important mechanism by which UA reverses the MDR of CRC.

Keywords

• Ursolic acid
• Colorectal cancer
• Multidrug resistance
• Apoptosis
• Autophagy
• Mammalian target of rapamycin (mTOR)