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 Lew...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.展开更多
基金supported by the Nantong Youth Medical Research Fund, China (No. WQ2015066)the Scientific and Technological Project of Nantong Science and Technology Bureau (No. MS2015025).
文摘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.
