Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-ß1 signaling pathway.

ABSTRACT

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-ß1 (TGF-ß1), 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-ß1 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-ß1 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-ß1, 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-ß1 signaling pathway.