Emodin reverses 5-Fu resistance in human colorectal cancer via downregulation of PI3K/Akt signaling pathway.
Am J Transl Res. 2020 ;12(5):1851-1861. Epub 2020 May 15. PMID: 32509181
BACKGROUND: 5-Fu resistance is a major obstacle in the treatment of malignant tumors. Therefore, combination therapy is employed to overcome this limitation. Since it was demonstrated that emodin could resensitize breast cancer to 5-Fu treatment, we aimed to investigate if emodin could reverse 5-Fu resistant colorectal cancer (CRC) in the current study.
METHODS: For the aim to explore the effect of emodin on 5-Fu resistant CRC, 5-Fu-resistant cell line (SW480/5-Fu) was established. CCK-8 assay and Ki67 staining were performed to evaluate the effects of emodin in combination with 5-Fu on cell proliferation. Flow cytometry was used to detect the apoptosis of SW480/5-Fu cells. Additionally, the invasion and migration of SW480/5-Fu cells were tested by transwell assay and wound healing, respectively. Western-blot was performed to examine the protein expressions in SW480/5-Fu cells. Moreover, xenograft mice model was established to test the anti-tumor effect of emodin in combination with 5-Fu.
RESULTS: Emodin notably increased the anti-proliferation effect of 5-Fu in SW480/5-Fu cells. Similarly, the invasion and migration of SW480/5-Fu cells were further inhibited in the presence of emodin. In addition, the combination treatment (emodin plus 5-Fu) induced cell apoptosis via inhibiting Bcl-2 and activating cleaved caspase3 and Bax. Moreover, emodin reduced 5-Fu resistant in CRC via downregulation of PI3K/Akt signaling. Finally,study indicated that emodin could notably reverse 5-Fu resistance in CRC xenograft.
CONCLUSION: Our research revealed that emodin could reverse 5-Fu resistance in CRC through inactivating PI3K/Akt signaling pathwayand. Thus, this finding might provide a molecular basis for treating 5-Fu resistant CRC.