Efficient inhibition of growth of metastatic cancer cells after resection of primary colorectal cancer by soluble Flt-1

Tumour Biol. 2015 Sep;36(10):7399-407. doi: 10.1007/s13277-015-3434-y. Epub 2015 Apr 21.

Abstract

Removal of primary tumors often leads to increases in growth of metastatic tumor cells. Thus, development of an efficient treatment to inhibit the growth of metastatic tumor cells after resection of primary tumors appears to be critical for cancer therapy. Here, we reported that administration of a Chinese medicine Shiquandabutao (SQDBT) after removal of the primary cancer significantly inhibited the growth of metastatic cancer cells in mouse liver. Further analyses showed that the effect of SQDBT resulted from one of its main component, Siwutang (SWT), rather than from another main component, Sijunzitang (SJZT). Moreover, we found that the soluble Flt-1 from SWT neutralized the increased placental growth factor (PLGF) secreted by the metastatic cancer cells after primary cancer resection and subsequently inhibited the cancer neovascularization to suppress the metastatic cancer growth. Thus, our study reveals an essential role of SQDBT in inhibiting the growth of metastatic cancer after removal of primary cancer and further highlights PLGF as a potential target for metastatic cancer treatment.

Keywords: Colorectal cancer; Placental growth factor (PLGF); SJZT; SQDBT; SWT; Soluble Flt-1 (sFlt-1); Vascular endothelial growth factor A (VEGF-A).

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Blotting, Western
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Drugs, Chinese Herbal / administration & dosage*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Male
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / prevention & control*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Drugs, Chinese Herbal
  • RNA, Messenger
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1