目的 探讨皂角刺总黄酮体内外对小鼠肺癌的防治作用及其机制。方法 用不同质量浓度皂角刺总黄酮处理体外培养的小鼠Lewis肺癌细胞和L929胚肺成纤维细胞48 h，MTT法检测细胞增殖与黏附，划痕标记染料示踪技术观察细胞连接通讯的功能。将小鼠分成模型组、槲皮素（100 mg/kg）阳性对照组、皂角刺总黄酮高和低剂量（100、30 mg/kg）组，每周2次、连续5周ip乌拉坦制备小鼠肺癌模型，ip乌拉坦1次后开始给药，每天1次，连续给药10周，另设对照组。免疫组化法检测肺肿瘤部位间隙连接蛋白43（Cx43，）的表达。建立小鼠Lewis肺癌皮下移植模型和肺转移模型，实验设模型组、阿霉素（5 mg/kg）阳性对照组、皂角刺总黄酮高和低剂量组（100、30 mg/kg），模型建立后次日给药，连续给药3周，观察荷瘤小鼠存活时间。结果 皂角刺总黄酮可剂量相关性抑制体外培养的Lewis肺癌细胞增殖；降低Lewis肺癌细胞黏附，并以剂量相关方式促进Lewis肺癌细胞间连接通讯，但对L929胚肺成纤维细胞黏附无影响；对乌拉坦诱导小鼠肺癌有预防作用，增强Cx43的免疫组化染色强度；对Lewis肺癌皮下肿瘤及实验性肺转移均具有剂量相关性抑制作用，能延长荷瘤小鼠的存活时间。结论 皂角刺总黄酮能增强细胞连接通讯，选择性预防和治疗肺癌，是潜在抗肿瘤药物。

Objective To explore the prevention and treatment of total flavonoids from Gleditsiae Spina (TFGS) on lung cancer and its mechanisms. Methods Mouse Lewis lung cancer (LLC) and embryonic lung fibroblast (L929) cells were treated with different doses of TFGS for 48 h, cell proliferation and adhesion were examined by MTT assay, and gap junctional intercellual communication (GJIC) was measured through scrape loading and dye transfer. The mice were randomly divided into model, quercetin (100 mg/kg, positive control), high- and low-dose (100 and 30 mg/kg) TFGS groups. The mice were ip injected with urethane twice weekly for five weeks to induce lung carcinogenesis and treated once daily for 10 weeks following the first urethane injection. The prevention of TFGS on chemocarcinogenesis was evaluated and the expression of gap junctional protein connexin 43 (Cx43) in lung tissue with tumors was compared by immunohistochemistry. The LLC cells were injected into the lateral axilla and tail vein respectively to establish the LLC sc allograft and experimental lung metastasis. The tumor-inocubating mice were randomly divided into model, doxorubicin (5 mg/kg, positive control), high- and low-dose (same as above) TFGS groups. The mice received the treatment for three weeks following tumor inocubation, and the effects of TFGS on the tumor size, metastasis, and life span were evaluated. Results TFGS inhibited LLC cell proliferation in a dose dependent manner but had no effect on L929 cell proliferation in vitro. TFGS with a little effect on cell proliferation decreased cell adhesion and promoted GJIC in a dose dependent manner in LLC cells but did not affect the L929 cell adhesion. TFGS was able to prevent carcinogenesis induced by urethane and enhance Cx43 staining in lung region with tumor in immunohistochemistry. Compared with untreated model mice, GJIC reduced the tumor size and metastasis and prolongated life span in a dose dependent manner. Conclusion TFGS could promote GJIC to prevent and treat tumor and might be a potential antitumor agent.

国家自然科学基金资助项目（81173094）；河南省高校青年骨干教师项目（2010GGJS-025）；河南省科技厅重点攻关项目（112101310308）；河南大学省部共建项目（SBGJ090704）