Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
Front Immunol. 2023 Jun 22;14:1220165. doi: 10.3389/fimmu.2023.1220165. eCollection 2023.
Nausea and vomiting (CINV) are distressful and widespread side effects of chemotherapy, and additional efficient regimens to alleviate CINV are urgently needed. In the present study, colorectal cancer (CRC) mice model induced by Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to evaluate the cancer suppression and CINV amelioration effect of the combination of thalidomide (THD) and . Our results suggested that the combination of THD and abundantly enhanced the anticancer effect of cisplatin activating the caspase-3 apoptosis pathway, and also ameliorated CINV inhibiting the neurotransmitter (e.g., 5-HT and tachykinin 1) and its receptor (e.g., 5-HTR and NK-1R) in brain and colon. Additionally, the combination of THD and reversed the gut dysbacteriosis in CRC mice by increasing the abundance of , , , and at the genus level, and also led to increased expression of occludin and Trek1 in the colon, while decreased expression of TLR4, MyD88, NF-κB, and HDAC1, as well as the mRNA level of IL-6, IL-1β, and TNF-α. In all, these results suggest that the combination of THD and had good efficacy in enhancing cancer treatments and ameliorating CINV, which thus provides a more effective strategy for the treatment of CRC.
恶心和呕吐（CINV）是化疗的一种常见且令人不适的副作用，因此急需更有效的方案来缓解 CINV。本研究通过使用氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导结直肠癌（CRC）小鼠模型，评估了沙利度胺（THD）和 联合应用对顺铂的抗癌增效作用和止吐效果。结果表明，THD 和 联合应用可通过激活半胱天冬酶-3 凋亡途径显著增强顺铂的抗癌作用，同时抑制脑和结肠中的神经递质（如 5-HT 和速激肽 1）及其受体（如 5-HTR 和 NK-1R），从而改善 CINV。此外，THD 和 联合应用通过增加属水平的 、 、 和 的丰度，逆转了 CRC 小鼠的肠道菌群失调，并导致结肠中 occludin 和 Trek1 的表达增加，而 TLR4、MyD88、NF-κB 和 HDAC1 的表达以及 IL-6、IL-1β 和 TNF-α 的 mRNA 水平降低。综上所述，THD 和 联合应用在增强癌症治疗效果和缓解 CINV 方面具有良好的疗效，为 CRC 的治疗提供了更有效的策略。
