Background Cervical cancer is the most common malignancy of the female lower genital tract. In our previous study, we found that TLR4 promotes cervical cancer cell growth in vitro. The aim of this study was to further explore the role of TLR4 in HPV-related cervical cancer in vivo by using a nude mouse xenograft model. Methods Cervical cancer-derived HeLa and CaSki cells (5 × 10 7 /mL) were either stimulated with an optimal concentration of LPS for the appropriate time (HeLa cells were treated with 1 μg/mL LPS for 1 h, and CaSki cells were treated with 2 μg/mL LPS for 1.5 h) or transfected with TLR4 shRNA and then injected subcutaneously into the dorsal right posterior side of nude mice. The shortest width and longest diameter of the transplanted tumors in the nude mice were measured every 3 days.TLR4, IL-6,iNOS, IL-8,COX-2, MIP-3α, TGF-β1 and VEGF expression levels in the transplanted tumor tissue were detected by immunohistochemistry. Results The tumor formation rate was 100% in both HeLa and CaSki nude mouse groups. The tumors grew faster, and the cachexia symptoms were more serious in the LPS groups than in the control group. In contrast, the tumors grew slower, and the cachexia symptoms were milder in the TLR4-silenced groups. TLR4, iNOS, IL-6, MIP-3α and VEGF were highly expressed in the transplanted tumor tissues from the LPS groups, and their expression levels were decreased in the TLR4-silenced groups. Conclusion TLR4 expression is closely associated with the tumorigenesis and growth of HPV-positive cervical cancer; TLR4 promotes HPV-positive cervical tumor growth and facilitates the formation of a local immunosuppressive microenvironment. Eventually, these conditions may lead to cervical cancer development.

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TLR4对体内HPV相关宫颈癌生长及局部炎症微环境的影响

背景宫颈癌是女性下生殖道最常见的恶性肿瘤。在我们之前的研究中，我们发现TLR4在体外促进宫颈癌细胞的生长。本研究的目的是通过裸鼠异种移植模型进一步探讨TLR4在体内HPV相关宫颈癌中的作用。方法宫颈癌来源的HeLa和CaSki细胞（5×10 7 /mL）用最佳浓度的LPS刺激适当的时间（HeLa细胞用1 μg/mL LPS处理1 h，CaSki细胞用2 μg/mL LPS 1.5 h)或转染TLR4 shRNA后皮下注射至裸鼠背部右后侧。每3 d测定裸鼠移植瘤的最短宽度和最长直径。移植瘤中TLR4、IL-6、iNOS、IL-8、COX-2、MIP-3α、TGF-β1、VEGF的表达量采用免疫组织化学法检测肿瘤组织。结果HeLa和CaSki裸鼠组成瘤率均为100%。LPS组肿瘤生长较快，恶病质症状较对照组更严重。相比之下，TLR4沉默组的肿瘤生长较慢，恶病质症状较轻。TLR4、iNOS、IL-6、MIP-3α和VEGF在LPS组的移植瘤组织中高表达，而在TLR4沉默组中其表达水平降低。结论 TLR4表达与HPV阳性宫颈癌的发生、发展密切相关；TLR4促进HPV阳性宫颈肿瘤生长并促进局部免疫抑制微环境的形成。最终，这些情况可能导致宫颈癌的发展。