目的 探究苦参碱对肺癌放疗敏感性的影响和作用机制。方法 人非小细胞肺癌A549细胞分为对照组、2 Gy放疗组、4 Gy放疗组、苦参碱组、苦参碱联合2 Gy组、苦参碱联合4 Gy组、甘氨双唑钠联合2 Gy组、甘氨双唑钠联合4 Gy组，通过克隆形成、细胞增殖、细胞凋亡评价苦参碱对A549细胞放疗敏感性的影响；建立裸鼠皮下移植瘤模型，分为对照组、5 Gy放疗组、苦参碱组、苦参碱联合5 Gy组、甘氨双唑钠联合5 Gy组，记录小鼠瘤体积；Western blotting法检测A549细胞和小鼠瘤组织中β-连环蛋白（β-catenin）、p21激活蛋白激酶6（p21-activated protein kinase，PAK6）、c-myc、半胱氨酸蛋白酶3（Caspase-3）的表达。结果 与单独放疗组相比，苦参碱联合放疗组A549细胞克隆形成、细胞增殖显著降低（P<0.001），细胞凋亡显著增加（P<0.001），裸鼠肿瘤体积显著降低（P<0.001），细胞和裸鼠肿瘤组织中PAK6、c-myc、磷酸化β-catenin蛋白表达显著下调（P<0.05、0.01、0.001），Caspase-3蛋白表达显著上调（P<0.001）。结论 苦参碱通过干扰PAK6表达，抑制Wnt/β-连环蛋白（Wnt/β-catenin）信号通路，从而提高肺癌的放疗敏感性。

Objective To explore the effect and mechanism of matrine on radiosensitivity of lung cancer. Methods Human non- small cell lung cancer A549 cells were divided into control group, 2 Gy radiotherapy group, 4 Gy radiotherapy group, matrine group, matrine combined with 2 Gy group, matrine combined with 4 Gy group, glycinazole sodium combined with 2 Gy group and glycinazole sodium combined with 4 Gy group; Clonal formation, cell proliferation, apoptosis were used to evaluate the effect of matrine on radiosensitivity of A549 cells. Subcutaneous transplantation tumor model in nude mice was established, which were divided into control group, 5 Gy radiotherapy group, matrine group, matrine combined with 5 Gy radiotherapy group, glycinazole sodium combined with 5 Gy radiotherapy group, tumor volume of mice were recorded; Western blotting was used to detect the expressions of β-catenin, p21-activated protein kinase (PAK6), c-myc and Caspase-3. Results Compared with radiotherapy group, the cell maturation and proliferation were significantly reduced (P < 0.001), cell apoptosis was significantly increased (P < 0.001), tumor volume of nude mice was reduced (P < 0.001), the expressions of PAK6, c-myc and phosphorylation-β-catenin on A549 cells and tumor tissues were significantly downregulated (P < 0.05, 0.01, 0.001), the expression of Caspase-3 was significantly increased (P < 0.001) in matrine combined with radiotherapy group. Conclusion Matrine could improve radiosensitivity of lung cancer through inhibiting the expression of PAK6 and Wnt/β-catenin signaling pathway.

R285.5

河南省科技攻关项目（116108351126）