Li Tonghu, Si Wenjun, Zhu Jiameng, Yin Li, Zhong Chongyang
Department of General Surgery, Shuyang Traditional Chinese Medicine Hospital Suqian 223600, Jiangsu, China.
Am J Transl Res. 2020 May 15;12(5):1851-1861. eCollection 2020.
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.
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 .
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.
Our research revealed that emodin could reverse 5-Fu resistance in CRC through inactivating PI3K/Akt signaling pathway and . Thus, this finding might provide a molecular basis for treating 5-Fu resistant CRC.
5-氟尿嘧啶耐药是恶性肿瘤治疗中的主要障碍。因此，采用联合治疗来克服这一局限性。由于已证明大黄素可使乳腺癌对5-氟尿嘧啶治疗重新敏感，我们旨在研究在本研究中大黄素是否能逆转5-氟尿嘧啶耐药的结直肠癌（CRC）。
为了探究大黄素对5-氟尿嘧啶耐药CRC的作用，建立了5-氟尿嘧啶耐药细胞系（SW480/5-Fu）。进行CCK-8测定和Ki67染色以评估大黄素与5-氟尿嘧啶联合对细胞增殖的影响。采用流式细胞术检测SW480/5-Fu细胞的凋亡情况。此外，分别通过Transwell测定和伤口愈合实验检测SW480/5-Fu细胞的侵袭和迁移能力。进行蛋白质免疫印迹法检测SW480/5-Fu细胞中的蛋白表达。此外，建立异种移植小鼠模型以测试大黄素与5-氟尿嘧啶联合的抗肿瘤作用。
大黄素显著增强了5-氟尿嘧啶对SW480/5-Fu细胞的抗增殖作用。同样，在存在大黄素的情况下，SW480/5-Fu细胞的侵袭和迁移进一步受到抑制。此外，联合治疗（大黄素加5-氟尿嘧啶）通过抑制Bcl-2并激活裂解的caspase3和Bax诱导细胞凋亡。此外，大黄素通过下调PI3K/Akt信号通路降低CRC中的5-氟尿嘧啶耐药性。最后，研究表明大黄素可显著逆转CRC异种移植中的5-氟尿嘧啶耐药性。
我们的研究表明，大黄素可通过使PI3K/Akt信号通路失活来逆转CRC中的5-氟尿嘧啶耐药性。因此，这一发现可能为治疗5-氟尿嘧啶耐药的CRC提供分子基础。
