Shi Yangqian, Meng Lingyu, Zhang Chunliang, Zhang Fengmin, Fang Yong
Department of Microbiology, Harbin Medical University, Harbin, China.
Department of Microbiology, Harbin Medical University, Harbin, China; Wu Lien-Teh Institute, Harbin Medical University, Harbin, China; Heilongjiang Province Key Laboratory of Immunity and Infection, Pathogenic Biology, Harbin, China.
Microbiol Res. 2021 Nov 16;255:126921. doi: 10.1016/j.micres.2021.126921.
Colorectal cancer (CRC) is the third most common malignant tumor in the world. Previous research has shown that Lacticaseibacillus paracasei strains and its cultures have anti-colon cancer effects, but the study of L. paracasei-derived extracellular vesicles (LpEVs) as intercellular communication molecule against colon cancer has not been previously reported. Our research showed LpEVs were taken in by colorectal cancer cells. Subsequently, LpEVs inhibited the proliferation, migration, invasion and promote apoptosis of colorectal cancer cells. LpEVs inhibited the growth of CRC xenograft in nude mice and promoted tumor apoptosis in vivo. Transcriptome sequencing analysis revealed that differentially expressed genes were involved in the regulation of apoptosis. LpEVs significantly inhibited the phosphorylation level of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT in colorectal cancer cells and reduced the expression of Bcl-2 protein. In conclusion, extracellular vesicles of Lacticaseibacillus paracasei PC-H1 can inhibit the growth of colorectal cancer cells in vivo and vitro and induce apoptosis through PDK1/AKT/Bcl-2 signaling pathway. This research not only provides a new mechanism for the anti-tumor effects of probiotics, but also opens up new opportunity for the treatment of colon cancer.
结直肠癌（CRC）是全球第三大常见恶性肿瘤。先前的研究表明，副干酪乳杆菌菌株及其培养物具有抗结肠癌作用，但此前尚未有关于副干酪乳杆菌来源的细胞外囊泡（LpEVs）作为抗结肠癌的细胞间通讯分子的研究报道。我们的研究表明，LpEVs被结肠癌细胞摄取。随后，LpEVs抑制结肠癌细胞的增殖、迁移、侵袭并促进其凋亡。LpEVs抑制裸鼠体内CRC异种移植物的生长并促进体内肿瘤凋亡。转录组测序分析显示，差异表达基因参与了凋亡调控。LpEVs显著抑制结肠癌细胞中3-磷酸肌醇依赖性蛋白激酶-1（PDK1）和AKT的磷酸化水平，并降低Bcl-2蛋白的表达。总之，副干酪乳杆菌PC-H1的细胞外囊泡可在体内外抑制结肠癌细胞的生长，并通过PDK1/AKT/Bcl-2信号通路诱导细胞凋亡。本研究不仅为益生菌的抗肿瘤作用提供了新机制，也为结肠癌的治疗开辟了新途径。
