[摘 要] 目的：探讨多能蛋白聚糖（VCAN）和基质金属蛋白酶9（MMP9）在肺腺癌（LUAD）侵袭与转移中的作用及其调控机 制。方法：收集30例LUAD及配对癌旁组织，采用免疫组织化学（IHC）法检测VCAN和MMP9表达；另以人LUAD细胞NCI H1975和A549为模型，运用siRNA干扰和质粒过表达技术，结合挽救实验，采用CCK-8、划痕愈合实验及Transwell实验评估细胞 增殖、迁移与侵袭能力，RT-qPCR及WB法检测基因和蛋白表达。结果：VCAN和MMP9在LUAD组织中的表达均显著高于癌 旁组织（均P < 0.001），且H-score随肿瘤分期的进展呈递增趋势（均P < 0.01）。体外实验表明，si-VCAN显著降低VCAN和 MMP9的mRNA及蛋白水平，抑制细胞活力、迁移和侵袭（均P < 0.01）；过表达MMP9则显著增强上述恶性表型（均P < 0.001），并 可被si-VCAN逆转（均P < 0.01），而MMP9沉默对VCAN蛋白表达无显著影响（P > 0.05）。结论：VCAN通过上调MMP9表达促 进LUAD细胞的增殖、迁移和侵袭，VCAN/MMP9轴可能成为LUAD治疗的潜在靶点。

[Abstract] Objective: To investigate the roles and regulatory mechanisms of versican (VCAN) and matrix metalloproteinase-9 (MMP9) in the invasion and metastasis of lung adenocarcinoma (LUAD). Methods: Thirty LUAD specimens and their matched adjacent non-tumor tissues were collected. Immunohistochemistry (IHC) was performed to detect VCAN and MMP9 expressions. Human LUAD cell lines NCI-H1975 and A549 were employed as models. siRNA interference and plasmid overexpression, combined with rescue assays, were applied. Cell proliferation, migration, and invasion abilities were evaluated by CCK-8, scratch-healing assay, and Transwell assay, respectively. Gene and protein expression were detected by RT-qPCR and WB assay. Results: VCAN and MMP9 were significantly up-regulated in LUAD tissues compared with those in adjacent non-tumor tissues (both P < 0.001), and their H-score increased progressively with advancing tumor stage (both P < 0.01). In vitro experiments revealed that si-VCAN markedly reduced VCAN and MMP9 mRNA and protein levels and suppressed cell viability, migration, and invasion (all P < 0.01), whereas MMP9 overexpression significantly promoted these malignant phenotypes (all P < 0.001); these effects were reversed by si-VCAN (all P < 0.01). MMP9 knockdown did not significantly affect VCAN protein levels (P > 0.05). Conclusion: VCAN enhances the proliferation, migration, and invasion of LUAD cells by up-regulating MMP9. The VCAN/MMP9 axis may represent a potential therapeutic target for LUAD.

湖北省卫生健康委科研项目（No. WJ2023M148）；武汉市 卫生科研基金（No. WZ22Q01）；华中科技大学协和江北医院自由创 新预研基金（No. XHJBKXYJJJ-QNXM-06）