Wang Li, Li Fang, Gu Ni-Ni, Shen Hui, Han Cai-Li, Li Kai-Yang, Yan Rui-Yang, Wang Jue, Mi Zhi-Kuan
Medical School of Yan'an University Yan'an 716000, China.
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(2):517-524. doi: 10.19540/j.cnki.cjcmm.20221014.703.
In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.
近年来，结直肠癌（CRC）的临床治疗取得了很大进展，但化疗耐药性仍是降低结直肠癌患者生存率的主要原因之一。因此，改善化疗耐药性是亟待解决的问题。本研究旨在探讨羟基红花黄色素A（HSYA）在结直肠癌细胞增殖、迁移及对5-氟尿嘧啶（5-FU）化疗耐药中的调控作用及相关分子机制。本研究以HCT116和HT-29细胞为研究对象。首先，采用甲基噻唑基四氮唑蓝（MTT）法和集落形成试验检测并分析HSYA对结直肠癌细胞增殖的影响。其次，通过细胞周期检测分析HSYA对结直肠癌细胞周期的影响。此外，采用划痕试验和Transwell试验分析HSYA对结直肠癌细胞迁移的影响。在此基础上，探讨并分析HSYA对结直肠癌细胞5-FU化疗耐药性的影响及相关分子机制。结果显示，HSYA显著抑制结直肠癌细胞的增殖和迁移，并使细胞周期停滞于G_0/G_1期。此外，HSYA显著改善结直肠癌细胞对5-FU的化疗耐药性。吖啶橙染色和蛋白质免疫印迹结果显示，HSYA与5-FU联合治疗组结直肠癌细胞的自噬活性显著高于5-FU单药治疗组。与5-FU单药治疗组相比，HSYA与5-FU联合治疗组蛋白激酶B（Akt）和雷帕霉素靶蛋白（mTOR）的磷酸化水平显著降低，表明联合治疗组结直肠癌细胞中Akt/mTOR信号通路下调。综上所述，HSYA可能通过Akt/mTOR信号通路上调自噬活性，从而抑制结直肠癌细胞的增殖和迁移，并改善对5-FU的化疗耐药性。
