Zheng Yu, Lu Chang, Jiang Yong, Wei Nina, Chang Chenqi, Li Weidong, Chen Linwei, Chen Rui, Chen Zhipeng
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Department of Pharmacy, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, China.
Department of Pharmacy, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, China.
J Ethnopharmacol. 2025 Jan 31;340:119156. doi: 10.1016/j.jep.2024.119156. Epub 2024 Nov 28.
Gekko swinhonis Guenther, commonly referred to as Gecko in the following text, belongs to the genus Gekko within the family Gekko. Its dried whole body is a widely utilized traditional Chinese medicine, demonstrating significant efficacy in the treatment of gastrointestinal malignancies, particularly gastric cancer (GC). Nevertheless, the composition of the gecko is complex, necessitating further research into its active ingredients for the treatment of GC.
Isolation and characterization of the most active components in Gecko based on their anti-GC mechanisms of vascular endothelial cell inhibition and anti-neovascularization.
We utilized the enzymatic hydrolysate of Geckos to investigate its effectiveness and underlying mechanisms. Initially, we assessed its efficacy in ectopic and in-situ GC tumor-bearing mouse models. Subsequently, we evaluated the effectiveness of peptides, aliphatics, and small molecules derived from Gecko using CCK-8 and 3D tumor spheroid assays. The activities of peptides S1-S4 were further examined through these experiments. Finally, we screened, synthesized, and investigated five potential peptides for their pharmacodynamics in the CCK-8 assay and in the in-situ GC model mice.
The Gecko can inhibit the formation of blood vessels in the tumor microenvironment, providing a localized treatment for GC. The peptide components significantly inhibit vascular endothelial cells and impede the formation of new blood vessels, with the S2 peptide sections (0.3 KD - 3 KD) demonstrating the most potent inhibitory activity against angiogenesis. One of the active peptides effectively suppresses the growth of in-situ GC in nude mice through angiogenesis inhibition and also modulates immunity, all while exhibiting excellent biosafety.
We have achieved a significant breakthrough in the local treatment of GC using Gecko. Through pharmacodynamic experiments and a systematic process of isolation and identification, we identified the most effective anti-GC ingredients of Gecko, based on their mechanisms of inhibiting vascular endothelial cells and promoting anti-angiogenesis. Furthermore, we synthesized a lead peptide that demonstrates promising therapeutic efficacy and safety.
壁虎（以下文本中简称壁虎）属于壁虎科壁虎属。其干燥全体是一种广泛应用的传统中药，在治疗胃肠道恶性肿瘤，尤其是胃癌（GC）方面显示出显著疗效。然而，壁虎的成分复杂，需要进一步研究其治疗GC的活性成分。
基于壁虎对血管内皮细胞的抑制和抗血管生成的抗GC机制，分离和鉴定其最具活性的成分。
我们利用壁虎的酶解产物来研究其有效性及潜在机制。首先，我们在异位和原位GC荷瘤小鼠模型中评估其疗效。随后，我们使用CCK-8和3D肿瘤球体测定法评估源自壁虎的肽、脂肪族化合物和小分子的有效性。通过这些实验进一步检测了肽S1-S4的活性。最后，我们筛选、合成并在CCK-8测定法和原位GC模型小鼠中研究了五种潜在肽的药效学。
壁虎可抑制肿瘤微环境中的血管形成，为GC提供局部治疗。肽成分显著抑制血管内皮细胞并阻碍新血管形成，其中S2肽段（0.3 KD - 3 KD）对血管生成的抑制活性最强。一种活性肽通过抑制血管生成有效抑制裸鼠原位GC的生长，还可调节免疫，同时表现出优异的生物安全性。
我们在使用壁虎进行GC局部治疗方面取得了重大突破。通过药效学实验以及系统的分离和鉴定过程，基于其抑制血管内皮细胞和促进抗血管生成的机制，我们确定了壁虎最有效的抗GC成分。此外，我们合成了一种先导肽，其显示出有前景的治疗效果和安全性。
