Ying Jun, Zhou Haiyang, Wang Zhiguo, You Qing, Chen Junnan, Lu Hao, Zhang Jian
Division of Colorectal Surgery, Department of Surgery, Second Affiliated Hospital of Naval Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
Cancer Cell Int. 2023 Jan 16;23(1):6. doi: 10.1186/s12935-023-02847-4.
Chemotherapy resistance is an important bottleneck affecting the efficacy of chemotherapy in colon cancer. Therefore, improving the chemotherapy sensitivity of colorectal cancer cells is of great significance for improving the prognosis of patients with colon cancer.
CCK-8 assay was employed to examine the cell viability of colorectal cancer cell lines. Realtime-PCR and western blot were used to explore toll-like receptor 4 (TLR4) expression in colorectal cancer cell lines. The functions of TLR4 in the stemness of the colorectal cancer cell lines were analyzed by infecting cells with lentivirus containing TLR4 siRNA.
We found that aspirin could effectively enhance the chemosensitivity of CT26 and HCT116 colorectal cancer cell lines. Aspirin can also inhibit the stemness of colorectal cancer cell including inhibiting the number of clone formation and reducing the volume and number of cell spheres and inducing the down-regulation of stemness-related genes. Besides that, aspirin also lead to down-regulation of TLR4 expression in colorectal cancer cells. The TLR4 positive colorectal cancer cells demonstrated a higher chemotherapy resistance potential than TLR4 negative colorectal cancer cells. In addition, the stemness of TLR4 positive colorectal cancer cells is stronger than TLR4 negative colorectal cancer cells.
The results of our study indicate that aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4.
化疗耐药是影响结肠癌化疗疗效的重要瓶颈。因此,提高大肠癌细胞的化疗敏感性对改善结肠癌患者的预后具有重要意义。
采用CCK-8法检测大肠癌细胞系的细胞活力。运用实时荧光定量PCR和蛋白质免疫印迹法探究大肠癌细胞系中Toll样受体4(TLR4)的表达情况。通过用携带TLR4小干扰RNA的慢病毒感染细胞,分析TLR4在大肠癌细胞系干性中的作用。
我们发现阿司匹林能有效增强CT26和HCT116大肠癌细胞系的化疗敏感性。阿司匹林还能抑制大肠癌细胞的干性,包括抑制克隆形成数量、减少细胞球的体积和数量以及诱导干性相关基因的下调。除此之外,阿司匹林还导致大肠癌细胞中TLR4表达下调。TLR4阳性的大肠癌细胞比TLR4阴性的大肠癌细胞表现出更高的化疗耐药潜能。此外,TLR4阳性的大肠癌细胞的干性比TLR4阴性的大肠癌细胞更强。
我们的研究结果表明,阿司匹林可提高大肠癌细胞的化疗敏感性并抑制Toll样受体4的表达。