[Effect of jianpi-jiedu formula on tumor angiogenesis-relevant genes expression in colorectal cancer].

Journal: Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
PMID: 28070042

Abstract

To investigate the effect of the jianpi-jiedu formula (JPJD) on the expression of angiogenesis-relevant genes in colon cancer.
 Methods: Crude extract was obtained from JPJD by water extract method. The effect of JPJD crude extract on colon cancer cell proliferation capacity was determined by MTT assays. The IC50 value was calculated by GraphPad Prism5 software. Affymetrix gene expression profiling chip was used to detect significant differences in expressions of genes after JPJD intervention, and pathway enrichment analysis was performed to analyze the differentially expressed genes. Ingenuity Pathway Analysis software was applied to analyze differentially expressed genes relevant to tumor angiogenesis based on mammalian target of rapamycin (mTOR) signaling pathway and then the network diagram was built. Western blot was used to verify the protein levels of key genes related to tumor angiogenesis.
 Results: JPJD crud extract inhibited the proliferation capacity in colon cancer cells. The IC50 values in 24, 48, and 72 hours after treatment were 13.060, 9.646 and 8.448 mg/mL, respectively. The results of chip showed that 218 genes significantly upgraded, and 252 genes significantly downgraded after JPJD treatment. Most of the genes were related to the function of biosynthesis, metabolism, cell apoptosis, antigen extraction, angiogenesis and so on. There were 12 differentially expressed angiogenesis genes. IPA software analysis showed that the JPJD downregulated expression of sphingomyelin phosphodiesterase 3 (SMPD3), VEGF, vascular endothelial growth factor A (VEGFA), integrin subunit alpha 1 (ITGA1), cathepsin B (CTSB), and cathepsin S (CTSS) genes, while upregulated expressions of GAB2 and plasminogen activator, urokinase receptor (PLAUR) genes in the colorectal cancer cell. Western blot results demonstrated that JPJD obviously downregulated expressions of phospho-mTOR (P-mTOR), signal transducer and activator of transcription 3 (STAT3), hypoxia inducible factor-1α (HIF-1α), and VEGF proteins, while obviously upregulated the level of phospho-P53 (P-P53) protein.
 Conclusion: JPJD may inhibit colorectal tumor angiogenesis through regulation of the mTOR-HIF-1α-VEGF signal pathway.

Authors

  • Dan Mao
    Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Sanlin Lei
    Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Jin'an Ma
    Department of Oncology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Li Shi
    Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Shaofan Zhang
    Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Jianhua Huang
    Hunan University of Traditional Chinese Medicine College of Pharmacy, Changsha 410028, China.
  • Xinyi Liu
    Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Dengfeng Ding
    Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Yingjin Zhang
    Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Lei Feng
    National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
  • Sifang Zhang
    Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.

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