Yang Huijie, Zhan Xiaoyan, Zhao Jia, Shi Wei, Liu Tingting, Wei Ziying, Li Hui, Hou Xiaorong, Mu Wenqing, Chen Yuanyuan, Zheng Congyang, Wang Zhongxia, Wei Shengli, Xiao Xiaohe, Bai Zhaofang
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
China Military Institute of Chinese Materia, The Fifth Medical Center of PLA General Hospital, Beijing, China.
Front Pharmacol. 2024 Aug 7;15:1369563. doi: 10.3389/fphar.2024.1369563. eCollection 2024.
With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry. Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor. Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity. SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of and laid a theoretical basis for its application in combating breast and colon cancer.
随着对免疫学理解的不断深入，越来越多的免疫疗法在癌症治疗领域得到探索和应用。环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白（cGAS-STING）通路作为天然免疫反应的关键要素，已被确定在癌症免疫治疗中起关键作用。我们评估了木脂素成分五味子丙素（SC）对4T1和MC38荷瘤小鼠的抗肿瘤作用，并通过RNA测序、qRT-PCR和流式细胞术研究了SC对cGAS-STING通路及抗肿瘤免疫的增强作用。我们的研究结果显示，SC在乳腺癌和结肠癌模型中均显著抑制肿瘤生长。这种对肿瘤生长的抑制归因于I型干扰素反应的激活以及肿瘤内T细胞和自然杀伤（NK）细胞数量的增加。此外，SC显著促进了顺铂诱导的cGAS-STING通路激活。与顺铂单药治疗相比，SC与顺铂联合治疗对肿瘤生长的抑制作用更强。化疗疗效的增强与I型干扰素反应的增强和抗肿瘤免疫力的增强有关。研究表明，SC通过增强I型干扰素反应激活和增强抗肿瘤免疫力来减少肿瘤生长并提高化疗敏感性，这丰富了对其抗肿瘤免疫的研究，并为其在对抗乳腺癌和结肠癌中的应用奠定了理论基础。
