Cisplatin,Transforming growth factor-β1,Smad3,Smad7,Lung cancer,Drugs,Chinese herbal," /> Cisplatin,Transforming growth factor-β1,Smad3,Smad7,Lung cancer,Drugs,Chinese herbal,"/> Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway
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Journal of Integrative Medicine ›› 2017, Vol. 15 ›› Issue (3): 242-251.doi: 10.1016/S2095-4964(17)60330-3

• Research Article • Previous Articles     Next Articles

Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway

Shui-jie Shena,b, Yong-hong Zhanga, Xiao-xia Gub, Shui-ju Jiangc, Ling-jun Xub   

  1. The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu Province, China
    b Department of Oncology, Nantong Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nantong 226000, Jiangsu Province, China
    c Department of Respiratory Medicine, Nantong Third People’s Hospital, Nantong 226006, Jiangsu Province,China
  • Received:2016-11-13 Accepted:2017-01-04 Online:2017-05-15 Published:2017-05-15
  • Contact: Yong-hong Zhang, MD; E-mail: zyhong311@126.com
  • Supported by:
    This work was supported by the Nantong Youth Medical Research Fund, China (No. WQ2015066) and the Scientific and Technological Project of Nantong Science and Technology Bureau (No. MS2015025).

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.

Key words: Cisplatin, Transforming growth factor-β1, Smad3, Smad7, Lung cancer, Drugs, Chinese herbal

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