Kim Seung-Woo, Kim Chan Woo, Kim Hong Seok
Department of Biomedical Sciences, Inha University College of Medicine, Incheon, Republic of Korea.
Cancer Immunotherapy Evaluation Team, Non-Clinical Evaluation Center, Osong Medical Innovation Foundation (KBIO Health), Cheongju, Republic of Korea.
Anim Cells Syst (Seoul). 2024 Feb 9;28(1):55-65. doi: 10.1080/19768354.2024.2315950. eCollection 2024.
Breast cancer is a frequently occurring malignant tumor that is one of the leading causes of cancer-related deaths in women worldwide. Monoclonal antibodies that block programed cell death 1 (PD-1)/programed cell death ligand 1 (PD-L1) - a typical immune checkpoint - are currently the recommended standard therapies for many advanced and metastatic tumors such as triple-negative breast cancer. However, some patients develop drug resistance, leading to unfavorable treatment outcomes. Therefore, other approaches are required for anticancer treatments, such as downregulation of PD-L1 expression and promotion of degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from that exhibits antitumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been confirmed yet. This study aimed to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results show that SCO downregulated PD-L1 expression in a dose-dependent manner, via AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression, but increased the expression of mitogen-activated protein kinase phosphatase-3 (MKP-3). In addition, the SCO-induced decrease in PD-L1 expression was reversed by siRNA-mediated MKP-3 knockdown. Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.
乳腺癌是一种常见的恶性肿瘤，是全球女性癌症相关死亡的主要原因之一。阻断程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1（PD-L1）——一种典型的免疫检查点——的单克隆抗体，目前是许多晚期和转移性肿瘤（如三阴性乳腺癌）的推荐标准疗法。然而，一些患者会产生耐药性，导致治疗效果不佳。因此，抗癌治疗需要其他方法，如下调PD-L1表达和促进PD-L1降解。滨蒿内酯（SCO）是一种从[具体来源未给出]中分离出的具有抗肿瘤活性的生物活性化合物。然而，SCO对癌症中PD-L1表达的影响尚未得到证实。本研究旨在评估SCO在体外乳腺癌细胞中对PD-L1表达的作用。我们的结果表明，SCO通过抑制AKT以剂量依赖的方式下调PD-L1表达。有趣的是，SCO处理并未改变PTEN表达，但增加了丝裂原活化蛋白激酶磷酸酶-3（MKP-3）的表达。此外，siRNA介导的MKP-3敲低逆转了SCO诱导的PD-L1表达降低。总的来说，这些发现表明SCO通过上调MKP-3表达抑制乳腺癌细胞中PD-L1的表达。因此，SCO可能作为一种创新的癌症免疫治疗联合药物。
