Abstract
BackgroundCervical 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.MethodsCervical cancer-derived HeLa and CaSki cells (5 × 107/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.ResultsThe 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.ConclusionTLR4 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.
Highlights
Cervical cancer is the most common malignancy of the female lower genital tract
Toll-like receptor 4 (TLR4) was highly expressed in transplanted tumor tissue from the LPS-stimulated group and downregulated in that from the TLR4-silenced group Because the purpose of this study was to observe the effects of different TLR4 levels on the growth and other indexes of xenograft tumors, the first step was to determine whether certain experimental treatments could alter TLR4 levels in the transplanted tumor tissues to ensure the validity of the subsequent experiments
TLR4 promotes the growth of tumors transplanted in nude mice When nude mice were injected on the dorsal right posterior side with HeLa and CaSki cells subjected to different treatments, tumors gradually formed; the tumor formation rate was 100%
Summary
Cervical cancer is the most common malignancy of the female lower genital tract. 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 × 107/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 injected subcutaneously into the dorsal right posterior side of nude mice. High-risk types of HPV, especially HPV18 and HPV16, promote the tumorigenesis and progression of the majority of cervical cancers [6]. Researchers have identified that E6 can induce p53 degradation by binding to the ubiquitin ligase E6AP, inhibit p53-dependent signaling upon stress stimuli, and contribute to tumorigenesis
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