Yan Xijing, Yu Haoyuan, Liang Jinliang, Hu Zhongying, Li Xuejiao, Liu Huanyi, Yao Jia, Sui Xin, Zheng Jun, Li Rong
Department of Hepatic Surgery and Liver Transplantation Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Cell Death Discov. 2023 Nov 16;9(1):416. doi: 10.1038/s41420-023-01664-y.
It has been established that monotherapy yields limited efficacy in treating hepatocellular carcinoma (HCC), especially advanced HCC. Increasing evidence from preclinical studies and clinical trials indicates that combining multiple drugs can potentially refine treatment efficacy. Accordingly, it is crucial to explore more effective clinically feasible combination therapies to enhance the treatment outcomes of HCC patients. This study evaluated the antitumor efficacy and safety of combination therapy involving aspirin and lenvatinib in HCC. Through in vitro and in vivo assays, we demonstrated that this combination yielded stronger antitumor effects compared to lenvatinib or aspirin monotherapy. Furthermore, no significant adverse events were observed in an HCC mouse model during treatment. Mechanistic studies revealed that aspirin plus lenvatinib could target multiple oncogenes and tumor suppressors, affecting diverse signaling pathways in various biological processes conducive to antitumor effects. Overall, our findings suggest that aspirin plus lenvatinib could serve as a promising combination regimen to improve the therapeutic outcomes of HCC.
已经证实，单一疗法在治疗肝细胞癌（HCC），尤其是晚期HCC方面疗效有限。来自临床前研究和临床试验的越来越多的证据表明，联合使用多种药物可能会提高治疗效果。因此，探索更有效的临床可行联合疗法以提高HCC患者的治疗效果至关重要。本研究评估了阿司匹林和乐伐替尼联合治疗HCC的抗肿瘤疗效和安全性。通过体外和体内试验，我们证明这种联合疗法比乐伐替尼或阿司匹林单一疗法产生更强的抗肿瘤作用。此外，在治疗期间，HCC小鼠模型中未观察到明显的不良事件。机制研究表明，阿司匹林加乐伐替尼可以靶向多种癌基因和肿瘤抑制因子，影响各种生物过程中有助于抗肿瘤作用的不同信号通路。总体而言，我们的研究结果表明，阿司匹林加乐伐替尼可作为一种有前景的联合治疗方案，以改善HCC的治疗效果。
