芪玉三龙汤对肺癌移植瘤小鼠PI3K/Akt/mTOR通路PI3K、Akt、mTOR表达的影响

Effect of Qiyu Sanlong Decoction on Expression of PI3K,Akt,and mTOR in PI3K/Akt/mTOR Signaling Pathway in Mouse Model of Lung Cancer Xenograft

目的研究芪玉三龙汤对小鼠皮下移植瘤生长及对PI3K/Akt/mTOR信号通路调节的影响。方法采用Lewis肺癌细胞培养移植法复制肺癌荷瘤小鼠模型,荷瘤成功后随机分为模型组,化学治疗组,芪玉三龙汤高、中、低剂量组,联合组;观察小鼠的生存状态,绘制肿瘤生长曲线,计算抑瘤率;Western blot法检测荷瘤小鼠肿瘤组织PI3K、Akt、mTOR蛋白表达。结果芪玉三龙汤高剂量组、联合组生存状态优于化学治疗组;芪玉三龙汤对肺肿瘤具有温和的抑制作用,其高剂量抑制肿瘤生长作用较优,但量效关系不明显,其与顺铂联用无明显增效作用;芪玉三龙汤可以下调PI3K、Akt和mTOR表达水平,和顺铂联用对下调关键分子Akt的表达具有明显的协同作用。结论芪玉三龙汤对肺癌移植瘤的抑制作用可能与调控PI3K/Akt/mTOR信号通路关键分子有关,与化学治疗药联用可协同下调关键蛋白Akt的表达。

Objective To observe the effect of Qiyu Sanlong （QYSL） Decoction on the growth of subcutaneous xenograft and regulation of PI3K/Akt/mTOR signaling pathway in mice bearing lung cancer. Methods The mouse model of lung cancer xenograft was established using Lewis lung carcinoma （LLC） cells. After the successful establishment of the model, the mice were randomly divided into model group, chemotherapy group, high-, medium-, and low-dose QYSL Decoction groups, and combination group. Survival was observed in each group, the curve for tumor growth was plotted, and the tumor inhibition rate was calculated; Western blot was applied to measure the protein expression of phosphoinositide 3-kinase （PI3K）, Akt, and mammalian target of rapamycin （roTOR） in tumor tissue. Results The high-dose QYSL Decoction group and the combination group had a better survival compared with the chemotherapy group; QYSL Decoction mildly inhibited lung tumor, and high-dose QYSL Decoction had a better inhibito- ry effect on tumor growth compared with other doses of QYSL Decoction, but without significant doseeffect relationship, and its combination with cisplatin had no significant synergistic effect; QYSL Decoc- tion downregulated the protein expression of PI3K, Akt, and mTOR, and its combination with cisplatin had a significant synergistic effect in the downregulation of the key molecule Akt. Conclusion The inhibitory effect of QYSL Decoction on lung cancer xenograft may be related to the regulation of key molecules in the PI3K/Akt/mTOR signaling pathway, and a combination of QYSL Decoction and chemotherapeutic agents has a synergistic effect in the downregulation of the key protein Akt.