سابِق|تال

Jianpi Xiaoai Prescription Ameliorates Chemotherapy Resistance in Colon Cancer by Targeting FGF2 to Inhibit PI3K/Akt Signaling Pathway

  • role： First author第一作者
  • Affiliation：

    Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine，The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine，Changsha 410006，China

  • Email：jianxiaolan1988@126.com
  • Introduction：简小兰，博士，副主任医师，从事肿瘤病中西医结合防治方法和规律研究，E-mail：jianxiaolan1988@126.com
JIAN Xiaolan1,  
  • Affiliation：

    Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China

NING Kangwen2,  
  • Affiliation：

    Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China

YANG Jiaxiang2,  
  • Affiliation：

    Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China

KOU Shenglan2,  
  • Affiliation：

    Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China

KUANG Wanting2,  
  • Affiliation：

    Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China

WANG Ziqi2,  
  • Affiliation：

    Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China

TAN Yuqin2,  
  • Affiliation：

    Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine，The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine，Changsha 410006，China

ZENG Puhua1,  
  • role： Corresponding author通信作者
  • Affiliation：

    Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine，The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine，Changsha 410006，China

  • Email：418497975@qq.com
  • Introduction：谭玲娟，硕士，主治医师，从事肿瘤病中西医结合防治方法和规律研究，E-mail：418497975@qq.com；
TAN Lingjuan1*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine，The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine，Changsha 410006，China

  • Email：1289382701@qq.com
  • Introduction：彭巍，硕士，副主任医师，从事肿瘤病中西医结合防治方法和规律研究，E-mail：1289382701@qq.com
PENG Wei1*

ملخص

ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer.MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg-1）， 5-FU （0.02 g·kg-1）， JPXA+5-FU （15 g·kg-1+0.02 g·kg-1）， AZD4547 （0.012 5 g·kg-1）， and AZD4547+5-FU （0.012 5 g·kg-1+0.02 g·kg-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed.ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways.ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

مفهوم

Jianpi Xiaoai prescription;colorectal cancer;chemotherapy resistance;fibroblast growth factor;phosphatidylinositol-3-kinase/protein kinase B （PI3K/Akt）

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