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 in vivo. 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, in vivo 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 pathway in vitro and in vivo. Thus, this finding might provide a molecular basis for treating 5-Fu resistant CRC. AJTR
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 in vivo. 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, in vivo 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 pathway in vitro and in vivo. Thus, this finding might provide a molecular basis for treating 5-Fu resistant CRC. AJTR
Authors: Qing Zhang; Wen Wen Chen; Xue Sun; Die Qian; Dan Dan Tang; Li Lin Zhang; Mei Yan Li; Lin Yu Wang; Chun-Jie Wu; Wei Peng Journal: Int J Biol Sci Date: 2022-05-16 Impact factor: 10.750
Authors: Matheus Lohan-Codeço; Maria Luísa Barambo-Wagner; Luiz Eurico Nasciutti; Luis Felipe Ribeiro Pinto; Nathalia Meireles Da Costa; Antonio Palumbo Journal: Cell Mol Life Sci Date: 2022-02-03 Impact factor: 9.261