目的 探討皂角刺總黃酮體內(nèi)外對(duì)小鼠肺癌的防治作用及其機(jī)制。方法 用不同質(zhì)量濃度皂角刺總黃酮處理體外培養(yǎng)的小鼠Lewis肺癌細(xì)胞和L929胚肺成纖維細(xì)胞48 h，MTT法檢測(cè)細(xì)胞增殖與黏附，劃痕標(biāo)記染料示蹤技術(shù)觀察細(xì)胞連接通訊的功能。將小鼠分成模型組、槲皮素（100 mg/kg）陽性對(duì)照組、皂角刺總黃酮高和低劑量（100、30 mg/kg）組，每周2次、連續(xù)5周ip烏拉坦制備小鼠肺癌模型，ip烏拉坦1次后開始給藥，每天1次，連續(xù)給藥10周，另設(shè)對(duì)照組。免疫組化法檢測(cè)肺腫瘤部位間隙連接蛋白43（Cx43，）的表達(dá)。建立小鼠Lewis肺癌皮下移植模型和肺轉(zhuǎn)移模型，實(shí)驗(yàn)設(shè)模型組、阿霉素（5 mg/kg）陽性對(duì)照組、皂角刺總黃酮高和低劑量組（100、30 mg/kg），模型建立后次日給藥，連續(xù)給藥3周，觀察荷瘤小鼠存活時(shí)間。結(jié)果 皂角刺總黃酮可劑量相關(guān)性抑制體外培養(yǎng)的Lewis肺癌細(xì)胞增殖；降低Lewis肺癌細(xì)胞黏附，并以劑量相關(guān)方式促進(jìn)Lewis肺癌細(xì)胞間連接通訊，但對(duì)L929胚肺成纖維細(xì)胞黏附無影響；對(duì)烏拉坦誘導(dǎo)小鼠肺癌有預(yù)防作用，增強(qiáng)Cx43的免疫組化染色強(qiáng)度；對(duì)Lewis肺癌皮下腫瘤及實(shí)驗(yàn)性肺轉(zhuǎn)移均具有劑量相關(guān)性抑制作用，能延長(zhǎng)荷瘤小鼠的存活時(shí)間。結(jié)論 皂角刺總黃酮能增強(qiáng)細(xì)胞連接通訊，選擇性預(yù)防和治療肺癌，是潛在抗腫瘤藥物。

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.

國(guó)家自然科學(xué)基金資助項(xiàng)目（81173094）；河南省高校青年骨干教師項(xiàng)目（2010GGJS-025）；河南省科技廳重點(diǎn)攻關(guān)項(xiàng)目（112101310308）；河南大學(xué)省部共建項(xiàng)目（SBGJ090704）