抗肺癌 1 号方联合顺铂通过转化生长因子-β1 信号通路抑制肺癌细胞生长。
Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway.
机构信息
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu Province, China.
Department of Oncology, Nantong Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nantong 226000, Jiangsu Province, China.
出版信息
J Integr Med. 2017 May;15(3):242-251. doi: 10.1016/S2095-4964(17)60330-3.
OBJECTIVE
To investigate the tumor inhibition effect of Yangfei Kongliu Formula (YKF), a compound Chinese herbal medicine, combined with cisplatin (DDP) and its action mechanisms.
METHODS
C57BL/6 mice with Lewis lung carcinoma were divided into six groups: control group (C), DDP group (2 mg/kg, DDP), low-dose YKF group (2.43 g/kg, L), high-dose YKF group (24.3 g/kg, H), low-dose YKF combined with DDP group (L + DDP) and high-dose YKF combined with DDP group (H + DDP). Transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3) and Smad7 levels were measured with quantitative real-time polymerase chain reaction (qPCR), Western blotting and immunohistochemistry. An enzyme-linked immunosorbent assay was used to analyze the expressions of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α).
RESULTS
YKF combined with DDP significantly inhibited the growth and metastasis of tumors relative to the control group, and YKF groups (P < 0.05). There was no significant difference between high-dose YKF group and low-dose YKF group (P > 0.05). We also found that the expression levels of TGF-β1 and Smad3 were both significantly decreased by YKF relative to the control group (P < 0.05). Furthermore, after treatment with YKF combined with DDP, the expression levels of TGF-β1 and Smad3 were decreased but the expression level of Smad7 was increased relative to the DDP group (P < 0.05). Compared to the DDP group, the combination of YKF and DDP enhanced the effect of tumor inhibition (P < 0.05), showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased serum levels of IL-2 and TNF-α relative to the control group (P < 0.05). Furthermore, the expression levels of IL-2 and TNF-α were significantly decreased when treated with YKF in combination with DDP. Co-treatment with YKF and DDP significantly inhibited tumor growth, decreased the expressions of TGF-β1, Smad3, IL-2 and TNF-α and increased the expression of Smad7; these differences were significant relative to both YKF groups and the control group (P < 0.05).
CONCLUSION
YKF can inhibit tumor growth synergistically with DDP, mainly through the TGF-β1 signaling pathway.
目的
研究复方中药养肺抗流方（YKF）联合顺铂（DDP）的抑瘤作用及其作用机制。
方法
将 C57BL/6 荷 Lewis 肺癌小鼠分为 6 组：对照组（C）、DDP 组（2 mg/kg，DDP）、低剂量 YKF 组（2.43 g/kg，L）、高剂量 YKF 组（24.3 g/kg，H）、低剂量 YKF 联合 DDP 组（L+DDP）和高剂量 YKF 联合 DDP 组（H+DDP）。采用实时荧光定量聚合酶链反应（qPCR）、Western blot 和免疫组织化学法检测转化生长因子-β1（TGF-β1）、母亲抗decapentaplegic 同源物 3（Smad3）和 Smad7 水平，酶联免疫吸附试验分析白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）的表达。
结果
与对照组相比，YKF 联合 DDP 能显著抑制肿瘤的生长和转移（P<0.05），且高、低剂量 YKF 组间差异无统计学意义（P>0.05）。我们还发现，与对照组相比，YKF 能显著降低 TGF-β1 和 Smad3 的表达水平（P<0.05）。此外，与 DDP 组相比，YKF 联合 DDP 治疗后 TGF-β1 和 Smad3 的表达水平降低，Smad7 的表达水平升高（P<0.05）。与 DDP 组相比，YKF 联合 DDP 增强了抑瘤作用（P<0.05），显示出 YKF 与 DDP 之间具有明显的协同作用。与对照组相比，DDP 或 YKF 治疗后血清 IL-2 和 TNF-α水平均降低（P<0.05）。此外，YKF 联合 DDP 治疗后，IL-2 和 TNF-α 的表达水平显著降低。YKF 联合 DDP 治疗可显著抑制肿瘤生长，降低 TGF-β1、Smad3、IL-2 和 TNF-α的表达水平，增加 Smad7 的表达水平；与 YKF 组和对照组相比，这些差异均有统计学意义（P<0.05）。
结论
YKF 可与 DDP 协同抑制肿瘤生长，主要通过 TGF-β1 信号通路。
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