Zheng Zhan, Wang Ju-yong, Xu Zhen-ye
Long-hua Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 Nov;29(11):1018-22.
To observe the effect of Feiyanning Granule (FYN) on tumor growth and cell cycle distribution in mice with Lewis lung cancer, as well as its influence on G1/S cell cycle checkpoint dominating signaling RB-E2F1 bio-axis.
Modeled C57BL/6 mice were randomly divided into 6 groups: the model group (A), the DDP treated group (B) peritoneally injected with cisplatin 0.1 mg on d1, d3 and d5 after modeling, and the 4 FYN treated groups (C-F), administered via gastrogavage with FYN Decoction, and FYN Granule in small-, median- and high- dose respectively for 14 days. The tumour inhibiting rate, tumour weight, and body weight of mice were observed after treatment; cell cycle distribution was detected by flow cytometry (FCM), RB-E2F1mRNA expressions in tumour tissue were analyzed by RT-PCR, and their protein expressions by Western blot.
Tumour weight in the 5 treated groups was lower than that in the model group (P < 0.05, P < 0.01). Body weight in group E was significantly higher than that in group A and B (P < 0.05, P < 0.01). FCM analysis showed the proportion of G0/G1 phase was higher in group E than in group A, B and C (P < 0.01), and cancer cell proliferation index (PI) in group E was lower than in group B (P < 0.05, P < 0.01). RT-PCR showed mRNA level of E2F1 was lower, but that of RB was significantly higher in group E than those in group A, B and C respectively (P < 0.01). Westem blot analysis showed the protein expression of E2F1 was lower in group E and B than that in group A (P < 0.05), while the protein expression of Rb in group E was higher than that in group A, B and C (P < 0.05).
The effect of FYN in inhibiting Lewis lung cancer growth was related to its intervention on cancer cell cycle distribution which blocks most tumor cells in G0/G1 phase. Moreover, FYN can reduce MDM2 expression, enhance P53 expression to influence cell cycle G1/S checkpoint dominating signaling, so as to achieve the effect of antagonizing lung cancer cell proliferation.
观察肺岩宁颗粒（FYN）对Lewis肺癌小鼠肿瘤生长及细胞周期分布的影响，以及对G1/S细胞周期关卡主导信号RB-E2F1生物轴的影响。
将造模后的C57BL/6小鼠随机分为6组：模型组（A）；顺铂治疗组（B），造模后第1、3、5天腹腔注射顺铂0.1mg；4个FYN治疗组（C-F），分别灌胃给予肺岩宁水煎剂、小剂量、中剂量和高剂量肺岩宁颗粒，连续给药14天。观察治疗后小鼠的抑瘤率、肿瘤重量及体重；采用流式细胞术（FCM）检测细胞周期分布，采用RT-PCR分析肿瘤组织中RB-E2F1mRNA表达，采用蛋白质免疫印迹法分析其蛋白表达。
5个治疗组的肿瘤重量均低于模型组（P<0.05，P<0.01）。E组小鼠体重显著高于A组和B组（P<0.05，P<0.01）。FCM分析显示，E组G0/G1期比例高于A组、B组和C组（P<0.01），E组癌细胞增殖指数（PI）低于B组（P<0.05，P<0.01）。RT-PCR显示，E组E2F1mRNA水平低于A组、B组和C组，而RB mRNA水平显著高于A组、B组和C组（P<0.01）。蛋白质免疫印迹分析显示，E组和B组E2F1蛋白表达低于A组（P<0.05），而E组Rb蛋白表达高于A组、B组和C组（P<0.05）。
肺岩宁抑制Lewis肺癌生长的作用与其干预癌细胞周期分布、使多数肿瘤细胞阻滞于G0/G1期有关。此外，肺岩宁可降低MDM2表达，增强P53表达，影响细胞周期G1/S关卡主导信号，从而达到拮抗肺癌细胞增殖的作用。
