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Abstract：
This study aimed to explore the role and mechanism of felodipine in lung cancer therapy. Murine subcutaneous lung squamous cancer (LUSC) models constructed by KLN-205 cells were utilized to assess the effect of felodipine monotherapy and in combination with the programmed cell death protein 1 antibody (PD1ab) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4ab). Immunohistochemistry analysis was subsequently applied to detect the number of CD8+ T cells and Ki67+ cells. Lastly, a series of in vitro and in vivo experiments were performed to evaluate the effects of felodipine on human LUSC cells and explore the preliminary mechanism underlying felodipine inhibition. The results revealed that felodipine monotherapy exerted a significant inhibitory effect on LUSC growth and synergistic antitumoral activity with PD1ab and CTLA4ab. Meanwhile, immunohistochemistry analysis displayed that felodipine promoted CD8+ T-cell infiltration and downregulated Ki67 expression in tumor cells. Moreover, in vitro and in vivo experiments utilizing human LUSC cells determined that felodipine impaired the proliferative and migratory abilities of cancer cells. In addition, TCGA data analysis uncovered that nuclear factor of activated T cell (NFAT1) expression was positively correlated with overall survival and disease-free survival. Finally, the cell counting kit-8 assay signaled that felodipine might suppress tumor growth by modulating NFAT1.
摘要：
本研究旨在探讨非洛地平在肺癌治疗中的作用及机制。利用由KLN-205细胞构建的小鼠皮下肺鳞状细胞癌(LUSC)模型来评估非洛地平单一疗法以及与程序性细胞死亡蛋白1抗体(PD1ab)和细胞毒性T淋巴细胞相关抗原-4(CTLA4ab)组合的效果。随后应用免疫组织化学分析来检测CD8+T细胞和Ki67+细胞的数量。最后,进行了一系列体外和体内实验，以评估非洛地平对人LUSC细胞的影响，并探索非洛地平抑制的初步机制。结果表明，非洛地平单一疗法对LUSC生长和PD1ab和CTLA4ab的协同抗肿瘤活性具有显着的抑制作用。同时,免疫组织化学分析显示，非洛地平促进肿瘤细胞中CD8+T细胞浸润并下调Ki67表达。此外，利用人LUSC细胞的体外和体内实验确定非洛地平损害了癌细胞的增殖和迁移能力。此外,TCGA数据分析发现，活化T细胞核因子（NFAT1）表达与总生存期和无病生存期呈正相关。最后,细胞计数试剂盒-8试验表明,非洛地平可能通过调节NFAT1抑制肿瘤生长.
