Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
department of breast surgery, Shanxi Provincial Cancer Hospital, Shanxi, China.
Biomed Pharmacother. 2023 Sep;165:115164. doi: 10.1016/j.biopha.2023.115164. Epub 2023 Jul 19.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasion and metastasis rates. Xian-Ling-Lian-Xia formula (XLLX) is a traditional Chinese medicine prescription widely used in China for treating TNBC. Clinical studies have shown that XLLX significantly reduces the recurrence and metastasis rate of TNBC and improves disease-free survival. However, the potential molecular mechanisms of XLLX on TNBC are not clear yet. Here, we investigated the effects of XLLX on TNBC using a mouse model and tumor cell lines. The results showed that XLLX significantly inhibited the proliferation, migration, and invasion abilities of TNBC cell lines MDA-MB-231 and 4T1 in vitro, induced apoptosis, and regulated the expression of proliferation, apoptosis, and EMT marker proteins in tumor cells. In in vivo experiments, XLLX treatment significantly reduced the progression of TNBC tumors and lung metastasis. Transcriptomics reveals that XLLX treatment significantly enriched differentially expressed genes in the peroxisome proliferator-activated receptor gamma (PPARγ) and AMP-dependent protein kinase (AMPK) signaling pathways. The western blot results confirmed that XLLX significantly upregulated the protein expression of PPARγ and p-AMPK in TNBC cells, tumors, and lung tissues. It is noteworthy that GW9662 (a PPARγ inhibitor) and Compound C (an AMPK inhibitor) partially reversed the anti-proliferation and anti-metastasis effects of XLLX in TNBC cells. Therefore, XLLX may effectively inhibit the growth and metastasis of TNBC by activating the PPARγ/AMPK signaling pathway.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，具有较高的侵袭和转移率。仙灵连消方（XLLX）是一种在中国广泛用于治疗 TNBC 的中药方剂。临床研究表明，XLLX 可显著降低 TNBC 的复发和转移率，提高无病生存率。然而，XLLX 对 TNBC 的潜在分子机制尚不清楚。在这里，我们使用小鼠模型和肿瘤细胞系研究了 XLLX 对 TNBC 的影响。结果表明，XLLX 显著抑制了体外 TNBC 细胞系 MDA-MB-231 和 4T1 的增殖、迁移和侵袭能力，诱导细胞凋亡，并调节肿瘤细胞中增殖、凋亡和 EMT 标志物蛋白的表达。在体内实验中，XLLX 治疗显著减缓了 TNBC 肿瘤的进展和肺转移。转录组学分析表明，XLLX 治疗显著富集了过氧化物酶体增殖物激活受体 γ（PPARγ）和 AMP 依赖的蛋白激酶（AMPK）信号通路中的差异表达基因。Western blot 结果证实，XLLX 显著上调了 TNBC 细胞、肿瘤和肺组织中 PPARγ 和 p-AMPK 的蛋白表达。值得注意的是，GW9662（PPARγ 抑制剂）和 Compound C（AMPK 抑制剂）部分逆转了 XLLX 对 TNBC 细胞的抗增殖和抗转移作用。因此，XLLX 可能通过激活 PPARγ/AMPK 信号通路有效抑制 TNBC 的生长和转移。
