Tumor metastasis is the main reason for the death of most cancer patients. C-X-C chemokine receptor type 4 (CXCR4) has been demonstrated to be overexpressed in numerous types of cancer. CXCR4 selectively binds with stromal cell-derived factor 1 (SDF1), also known as C-X-C family chemokine ligand 12 (CXCL12) (CXCL12/SDF-1), which induced tumor proliferation and metastasis. Recently, the use of conventional cancer treatments had some limitation; bacteria treatment for cancer becomes a trend that overcomes these limitations. Plenty of studies show that Salmonella has anti-tumor and anti-metastatic activity. The current study aimed to investigate Salmonella suppresses CXCR4 protein expression and tumor cell migration ability in B16F10 melanoma and LL2 lung carcinoma cells. Salmonella reduced CXCR4 protein expression through downregulating Protein Kinase-B (Akt)/Mammalian Target of Rapamycin (mTOR) signaling pathway. In cells transfected with constitutively active Akt plasmids, a reverse effect of Salmonella-induced inhibition of CXCR4 was observed. Tumor cells have chemotactic response to CXCL12 in migration assay, and we found that Salmonella reduced tumor chemotactic response after CXCL12 treatment. The C57BL/6 mice were intravenously injected with B16F10 and LL2 cells pre-incubated with or without Salmonella, the tumor size and lung weight of Salmonella group had obviously decreased, indicating anti-metastatic effect that confirmed the findings from the in vitro experiments.

中文翻译：

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沙门氏菌通过下调 CXC 趋化因子受体 4 型来减少肿瘤转移

肿瘤转移是大多数癌症患者死亡的主要原因。CXC 趋化因子受体 4 (CXCR4) 已被证明在多种癌症中过度表达。CXCR4 选择性结合基质细胞衍生因子 1 (SDF1)，也称为 CXC 家族趋化因子配体 12 (CXCL12) (CXCL12/SDF-1)，后者诱导肿瘤增殖和转移。最近，常规癌症治疗的使用有一些限制；癌症的细菌治疗成为克服这些限制的趋势。大量研究表明，沙门氏菌具有抗肿瘤和抗转移活性。目前的研究旨在研究沙门氏菌在 B16F10 黑色素瘤和 LL2 肺癌细胞中抑制 CXCR4 蛋白表达和肿瘤细胞迁移能力。沙门氏菌通过下调蛋白激酶 B (Akt)/哺乳动物雷帕霉素靶标 (mTOR) 信号通路来降低 CXCR4 蛋白表达。在用组成型活性 Akt 质粒转染的细胞中，观察到沙门氏菌诱导的 CXCR4 抑制的反向作用。肿瘤细胞在迁移试验中对CXCL12具有趋化反应，我们发现沙门氏菌在CXCL12处理后降低了肿瘤趋化反应。给C57BL/6小鼠静脉注射预孵育或未加入沙门氏菌的B16F10和LL2细胞，沙门氏菌组的肿瘤大小和肺重量均明显减小，表明抗转移作用证实了体外研究的结果 实验。