Lipopolysaccharide Activates Immunologic Defense against Colorectal Carcinoma in a Tumor Xenograft Model

Background. Lipopolysaccharides (LPS) are the major antigens expressed on the outer membrane of gram-negative bacteria. LPS induces a strong response in a normal immune system. Since tumor cells are suppressed by the immune system, immunotherapy is considered an efficient strategy against cancers. In this study, we assumed that LPS was able to activate the immune system to prevent tumor progression. Aims. We aim to investigate the potential anti-tumor effects of LPS on colorectal cancer (CRC) in a HCT-15 cells-derived tumor xenograft model. Methods. LPS was intravenously injected in the HCT15-derived tumor xenografts at day 7 and day 14, respectively, after tumor implantation for observing whether LPS was able to suppress tumor initiation and progression. Meanwhile, intravenous immunoglobulin (IVIG) was used to reduce immune response. The tumor volumes and body weight were recorded. Results. We found that LPS significantly reduced initial tumor growth (injected at day 7 with 100 mm^3 tumor size) in the HCT-15 bearing mice. Meanwhile, the anti-tumor effect was neutralized by co-injection of immunosuppressor IVIG. In addition, the body weight was recovered at day 14 in LPS group compared to PBS control group due to reduction of tumor volume in LPS group. We also found that LPS significantly eradicated tumor volume at later stage (injected at day 14 with 400mm^3 tumor size) but led to strong weight reduction. Conclusions. We demonstrated that LPS ameliorated small tumor initiation and big tumor progression in a CRC tumor xenograft model. The results suggested the immune system may be activated to suppress tumors. Limitations. The mouse model used in this study has normal immune function, but the immune activity in cancer patients is often inhibited by the tumor microenvironment. Therefore, whether LPS can induce the immune activity in cancer patients needs further investigation.

關鍵字

Colorectal cancer ； Lipopolysaccharides

並列摘要

背景：脂多醣（LPS）是革蘭氏陰性細菌外膜表達的主要抗原。LPS在正常免疫系統中誘導強烈反應。在這項研究中，我們假設LPS能夠激活免疫系統以防止腫瘤進展。方法：在腫瘤植入小鼠後第7天和第14天分別將LPS靜脈注射到HCT15衍生的異植腫瘤模型中，以觀察LPS是否能夠抑制腫瘤的發生和發展。結果：我們發現LPS顯著降低小鼠的初始腫瘤生長。同時，共同注射免疫抑製劑IVIG可中和抗腫瘤作用。由於注射LPS組有效抑制初始腫瘤生長，因此與PBS控制組相比，LPS組在第14天體重得以恢復。此外LPS可以根除較大的腫瘤，但體重卻顯著降低。結論：我們證明在CRC腫瘤異種移植模型中LPS改善了小腫瘤的發生和大腫瘤的進展。研究限制：此研究所用老鼠模型為正常免疫功能，但癌病人的免疫活性往往受到癌細胞微環境的抑制，因此，LPS是否可誘發癌病人的免疫活性需進一步探討。

並列關鍵字

大腸癌；脂多醣

參考文獻

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Lipopolysaccharide Activates Immunologic Defense against Colorectal Carcinoma in a Tumor Xenograft Model

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