Department of Medical Oncology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.
General Department, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.
Chem Biol Drug Des. 2024 Mar;103(3):e14507. doi: 10.1111/cbdd.14507.
Non-small cell lung cancer (NSCLC) is an aggressive and devastating cancer due to its metastasis induced by increased invasion. Lentinan is a polysaccharide exerting antitumor roles in multiple cancers, including lung cancer. However, the influence of lentinan on cell invasion in NSCLC remains unclear. Cell invasion was detected by transwell analysis. Matrix metallopeptidase 9 (MMP9) levels were measured through immunofluorescence staining. The markers arginase-1 (Arg-1), CD206 and interleukin (IL)-10 (IL-10) of M2 macrophages, Wnt3a, and β-catenin levels were measured by western blot or enzyme linked immunosorbent assay. Lentinan did not affect cell viability and proliferation in NSCLC cells. Lentinan suppressed cell invasion and reduced the expression and secretion of MMP9. Lentinan attenuated also M2 polarization of tumor-associated macrophages. Moreover, lentinan mitigated the M2 macrophage conditioned medium-mediated cell invasion and MMP9 alterations in NSCLC cells. Lentinan inhibited the activation of the Wnt/β-catenin signaling in NSCLC cells. The activated Wnt/β-catenin pathway reversed the suppressive effects of lentinan on cell invasion and MMP9 level in NSCLC cells. In conclusion, lentinan reduces cell invasion in NSCLC cells by inhibiting the M2 polarization of tumor-associated macrophages and the Wnt/β-catenin signaling.
非小细胞肺癌（NSCLC）是一种侵袭性和破坏性的癌症，因为其侵袭性增加导致转移。香菇多糖是一种在多种癌症中发挥抗肿瘤作用的多糖，包括肺癌。然而，香菇多糖对 NSCLC 细胞侵袭的影响尚不清楚。通过 Transwell 分析检测细胞侵袭。通过免疫荧光染色测量基质金属蛋白酶 9（MMP9）水平。通过 Western blot 或酶联免疫吸附试验测量 M2 巨噬细胞的标志精氨酸酶-1（Arg-1）、CD206 和白细胞介素（IL）-10（IL-10）、Wnt3a 和β-连环蛋白水平。香菇多糖对 NSCLC 细胞的活力和增殖没有影响。香菇多糖抑制细胞侵袭，降低 MMP9 的表达和分泌。香菇多糖还减弱了肿瘤相关巨噬细胞的 M2 极化。此外，香菇多糖减轻了 M2 巨噬细胞条件培养基介导的 NSCLC 细胞侵袭和 MMP9 改变。香菇多糖抑制了 NSCLC 细胞中 Wnt/β-连环蛋白信号通路的激活。激活的 Wnt/β-连环蛋白通路逆转了香菇多糖对 NSCLC 细胞侵袭和 MMP9 水平的抑制作用。总之，香菇多糖通过抑制肿瘤相关巨噬细胞的 M2 极化和 Wnt/β-连环蛋白信号通路来减少 NSCLC 细胞的侵袭。
