Hirata Marina, Nomura Tadashi, Inoue Yoshihiro H
Biomedical Research Center, Kyoto Institute of Technology, Kyoto 606-0962, Japan.
Graduate School of Science and Technology, Kyoto Institute of Technology, Kyoto 606-8585, Japan.
Cells. 2025 Mar 7;14(6):389. doi: 10.3390/cells14060389.
Five major antimicrobial peptides (AMPs) in are induced in () mutant larvae harboring lymph gland (LG) tumors, and they exhibit anti-tumor effects. The effects of other well-known AMPs, Cecropin A and Drosocin, remain unexplored. We investigated the tumor-elimination mechanism of these AMPs. A half-dose reduction in either the or gene reduced the induction of these AMPs and enhanced tumor growth in mutant larvae, indicating that their anti-tumor effects depend on the innate immune pathway. Overexpression of these AMPs in the fat body suppressed tumor growth without affecting cell proliferation. Apoptosis was promoted in the mutant but not in normal LGs. Conversely, knockdown of them inhibited apoptosis and enhanced tumor growth; therefore, they inhibit LG tumor growth by inducing apoptosis. The AMPs from the fat body were incorporated into the hemocytes of mutant but not normal larvae. Another AMP, Drosomycin, was taken up via phagocytosis factors. Enhanced phosphatidylserine signals were observed on the tumor surface. Inhibition of the signals exposed on the cell surface enhanced tumor growth. AMPs may target phosphatidylserine in tumors to induce apoptosis and execute their tumor-specific effects. AMPs could be beneficial anti-cancer drugs with minimal side effects for clinical development.
在携带淋巴腺（LG）肿瘤的（）突变幼虫中诱导产生了五种主要的抗菌肽（AMP），它们具有抗肿瘤作用。其他著名的AMP，如天蚕素A和果蝇抗菌肽的作用仍未得到研究。我们研究了这些AMP的肿瘤消除机制。在突变幼虫中，或者基因剂量减半会降低这些AMP的诱导，并增强肿瘤生长，这表明它们的抗肿瘤作用依赖于先天免疫途径。在脂肪体中过表达这些AMP可抑制肿瘤生长，而不影响细胞增殖。在突变的LG中促进了细胞凋亡，但在正常LG中未促进。相反，敲低它们会抑制细胞凋亡并增强肿瘤生长；因此，它们通过诱导细胞凋亡来抑制LG肿瘤生长。来自脂肪体的AMP被整合到突变幼虫而非正常幼虫的血细胞中。另一种AMP，果蝇霉素，是通过吞噬因子摄取的。在肿瘤表面观察到增强的磷脂酰丝氨酸信号。抑制细胞表面暴露的信号会增强肿瘤生长。AMP可能靶向肿瘤中的磷脂酰丝氨酸以诱导细胞凋亡并发挥其肿瘤特异性作用。AMP可能是具有最小副作用的有益抗癌药物，可用于临床开发。
