■三阴性乳腺癌(TNBC)是乳腺癌的侵袭性亚型。二甲双胍已被证明具有抑制恶性细胞增殖的潜力。本研究旨在探讨二甲双胍对TNBC中程序性死亡蛋白配体1(PD-L1)表达的调控作用及其机制。
■小鼠乳腺癌细胞系4T1与二甲双胍共培养,MTT法检测二甲双胍对细胞增殖的影响。二甲双胍对JNK表达的影响,MAPK通路卵白芯片检测RSK2和CREB。用敲低/过表达C-JunN末端激酶(JNK)的4T1细胞接种BALB/c小鼠,并给予二甲双胍。在实验结束时观察肿瘤组织的重量。免疫荧光染色观察PD-L1在肿瘤细胞中的表达,ELISA定量测定INF-γ水平。
■二甲双胍抑制4T1细胞的活力并增加JNK的磷酸化以减少RSK2和CREB的磷酸化。二甲双胍和JNK敲除降低肿瘤细胞中PD-L1的表达,但肿瘤组织重量无显著差异。二甲双胍可以降低肿瘤组织中INF-γ的水平,但JNK没有效果.
■二甲双胍可抑制三阴性乳腺癌小鼠PD-L1的表达,改善肿瘤微环境,但不能减小肿瘤的大小。
UNASSIGNED: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Metformin has been shown to have the potential to inhibit the proliferation of malignant cells. This study aimed to investigate the regulatory effect of metformin on the expression of programmed death protein ligand 1(PD-L1) and mechanisms in TNBC.
UNASSIGNED: Mouse breast cancer cell line 4T1 was co-cultured with metformin, and the effect of metformin on cell proliferation was detected by MTT assay. The effect of metformin on the expression of JNK, RSK2 and CREB was detected by MAPK pathway protein chip. BALB/c mice were inoculated with 4T1 cells with knockdown/overexpression of C-Jun N-terminal kinase (JNK), and administered with metformin. The weight of tumor tissue was observed at the end of the experiment. The expression of PD-L1 in tumor cells was observed by immunofluorescence staining and the level of INF-γwas quantitatively determined by ELISA.
UNASSIGNED: Metformin inhibited the viability of 4T1 cells and increased the phosphorylation of JNK to reduce the phosphorylation of RSK2 and CREB. Metformin and JNK knockdown reduced the expression of PD-L1 in tumor cells, but there was no significant difference in the weight of tumor tissue. Metformin can reduce the level of INF-γ in tumor tissues, but JNK has no effect.
UNASSIGNED: Metformin can inhibit the expression of PD-L1 in triple-negative breast cancer mice and improve the tumor microenvironment, but does not reduce the size of the tumor.