白桦脂酸诱导肺癌细胞凋亡，且不影响正常细胞生长，具有开发前景。NK细胞是机体抗肿瘤的第一道防线，抑制其表面的唾液酸结合性免疫球蛋白样凝集素7（Siglec-7）可增强NK细胞的杀伤活力。申请人近期研究发现，白桦脂酸增强共培养体系中NK细胞对肺癌细胞的杀伤活力，表面等离子共振实验表明白桦脂酸与Siglec-7特异性结合。由此推测：白桦脂酸通过结合Siglec-7从而增强NK细胞的抗肺癌效应。本项目拟利用含有光交联和生物素双功能基团的白桦脂酸分子探针明确其与Siglec-7的结合位点，基于微流控芯片细胞共培养、模拟肿瘤微环境的优势，阐明白桦脂酸增强NK细胞杀伤活力的分子机制，并用体内动物模型加以验证。本项目运用微流控芯片深入研究白桦脂酸增强NK细胞抗肺癌效应的分子机制，为肺癌免疫治疗的药物研发提供候选化合物，有助于白桦脂酸的开发和应用，为肿瘤免疫治疗提供新靶点，为肺癌药物研发提供新的技术平台。

Because of its selective cytotoxicity against lung cancer, betulinic acid (BA) is a very promising chemotherapeutic agent for the treatment of cancer. Natural killer (NK) cells have a central role in the innate immune response against cancer, inhibiting their surface inhibitory receptor sialic acid-binding immunoglobulin-like lectin (Siglec)-7 induces cytotoxicity by NK cells. Our recent studies reveal that BA enhances the killing effect of NK cells on lung cancer cells, indicating that BA is a potential immune booster. According to the surface plasmon resonance (SPR) assay, BA binds tightly to the Siglec-7 receptor. We hypothesize that the mechanism is determined by the specific binding of BA to Siglec-7. Here, we make a proposal by design and synthesis BA probes with dual photo-crosslinking/biotin bifunction groups to identify the potential binding structures. In addition, by conduction of microfluidic system, which can multicellular co-culture and better mimic in vivo conditions, we try to explore by what mechanism BA achieves such activity, further solidify our findings in mouse models, and elucidate possible mechanisms. This project is helpful to understand the molecular mechanism underlying how BA enhances the killing effect of NK cells on lung cancer, conductive to the development and clinical application of BA, and may provide an attractive pharmacological target for tumor immunetherapy and a platform for the discovery of anti-lung cancer drugs.