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Abstract：
Ovarian cancer poses a significant threat to women\'s health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM\'s apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. KEY POINTS: • This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins • The engineered bacteria can target and colonize tumor sites in vivo • VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells.
摘要：
卵巢癌对女性健康构成重大威胁,常规治疗方法遇到许多限制，新兴的工程细菌抗肿瘤策略为卵巢癌治疗提供了新的希望。在这项研究中,我们构建了VNP20009-Abvec-Igκ-MIIP（VM）工程菌株，并对其体外生长性能和迁移/侵袭抑制蛋白（MIIP）的表达能力进行了初步评估。随后，进行ID8卵巢癌细胞和小鼠癌症模型以研究VM对卵巢癌的影响。我们的结果表明，VM菌株表现出优异的生长性能，成功侵入ID8卵巢癌细胞，并表示MIIP，从而抑制细胞增殖和迁移。此外，VM特异性靶向肿瘤部位并表达MIIP,进一步缩小卵巢癌小鼠肿瘤体积(p<0.01),通过表皮生长因子受体（EGFR）的下调，拉斯，p-MEK,还有p-ERK.PI3K/AKT信号通路的下调和Bcl-2/Bax水平的降低也表明VM对卵巢癌细胞的凋亡潜能。总之,我们的研究表明，VM在体外和体内都表现出有希望的抗肿瘤作用，强调其临床治疗卵巢癌的潜力。关键点：•本研究构建了能够表达抗癌蛋白的鼠伤寒沙门氏菌工程菌株•工程细菌可以在体内靶向和定植肿瘤部位•VM可以抑制增殖，迁移,和卵巢癌细胞的侵袭。
