Aberrant β-catenin activation promotes the proliferation and survival of several types of tumor cells, including colorectal cancer (CRC) cells. Synthetic peptides are drug candidates for treating various diseases; however, peptide inhibitors of β-catenin have been rarely reported. A series of peptide inhibitors for β-catenin (F15A_1–9k, F15A_2–9k, and F15A_3–9k) were designed and synthesized, and then used to treat human CRC cells (HT-29). Next, a series of in vitro assays, including cell counting, colony formation, flow cytometry, and Transwell assays, were performed to assess the biological effects of the peptides on CRC cells. Mouse xenograft models of HT-29 tumors were also used to evaluate the inhibitory effect of the peptide inhibitors on β-catenin expression in vivo. The inhibitory effect of the peptide inhibitors on β-catenin production was tested in a confocal laser scanning microscope study (CLSMS), and by H&E, TUNEL, and immunohistochemical (IHC) staining. The peptide inhibitors significantly reduced the viability of HT-29 cells in time- and concentration-dependent manners. Moreover, the peptide inhibitors for β-catenin significantly inhibited CRC tumorigenesis both in vitro and in vivo. Mechanistically, the peptide inhibitors for β-catenin inhibited the angiogenesis activity of HT-29 cells. When administered by itself, F15A_2–9k blocked cell division, induced apoptosis, and reduced the migration and invasion capabilities of HT-29 cells, while a combination of F15A_1–9k, F15A_2–9k, and F15A_3–9k showed even stronger inhibitory effects on HT-29 cells. In summary, the peptides designed to inhibit β-catenin demonstrated anti-tumor activity both in vitro and in vivo, suggesting their potential as therapeutic agents for treating CRC.

β-catenin的异常激活可促进多种类型的肿瘤细胞（包括结直肠癌（CRC）细胞）的增殖和存活。合成肽是治疗各种疾病的候选药物；但是，很少有β-catenin的肽抑制剂报道。β-catenin的一系列肽抑制剂（F15A _1–9k，F15A _2–9k和F15A _3–9k进行了设计和合成，然后用于治疗人CRC细胞（HT-29）。接下来，进行了一系列体外测定，包括细胞计数，集落形成，流式细胞术和Transwell测定，以评估肽对CRC细胞的生物学作用。HT-29肿瘤的小鼠异种移植模型也用于评估肽抑制剂在体内对β-catenin表达的抑制作用。在共聚焦激光扫描显微镜研究（CLSMS）中，并通过H＆E，TUNEL和免疫组化（IHC）染色，测试了肽抑制剂对β-连环蛋白产生的抑制作用。肽抑制剂以时间和浓度依赖性方式显着降低HT-29细胞的活力。而且，β-连环蛋白的肽抑制剂在体外和体内均显着抑制CRC肿瘤发生。从机理上讲，β-catenin的肽抑制剂可抑制HT-29细胞的血管生成活性。单独给药时，F15A_2–9k阻止了细胞分裂，诱导了细胞凋亡，并降低了HT-29细胞的迁移和侵袭能力，而F15A _1–9k，F15A _2–9k和F15A _{3–9k的组合}显示出对HT-29的更强抑制作用29个单元格。总之，设计用于抑制β-catenin的肽在体外和体内均显示出抗肿瘤活性，表明它们作为治疗CRC的治疗剂的潜力。