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Updated: Apr 3, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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The malignant progression effects of regorafenib in human colon cancer cells

Chisato Tomida1, Kana Aibara, Naoko Yamagishi

  • 1Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School.

The Journal of Medical Investigation : JMI
|September 25, 2015
PubMed

Insights

Regorafenib, a VEGF-R inhibitor, can paradoxically promote colorectal cancer cell invasion and resistance to apoptosis. This suggests that blocking VEGF signaling may drive tumor malignancy and therapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Anti-angiogenic drugs targeting vascular endothelial growth factor receptors (VEGF-R) have advanced cancer therapy, particularly for colorectal cancer.
  • Acquired resistance to these therapies leads to disease progression, including invasion and metastasis, with underlying mechanisms remaining unclear.
  • A potential mechanism involves the direct effects of VEGF-R inhibitors on tumor cells expressing VEGF-R.

Purpose of the Study:

  • To investigate the direct effects of the VEGF-R inhibitor regorafenib on phenotype changes in colon cancer HCT116 cells.
  • To explore how regorafenib treatment influences cell migration, invasion, and apoptosis resistance.

Main Methods:

  • Treatment of colon cancer HCT116 cells with regorafenib.
  • Assessment of cell migration and invasion after short-term (2 days) and long-term (90 days) exposure.
  • Evaluation of resistance to hypoxia-induced apoptosis following chronic regorafenib exposure.

Main Results:

  • Short-term regorafenib treatment (2 days) activated cell migration and invasion compared to controls.
  • Chronic regorafenib exposure (90 days) dramatically increased migration and invasion.
  • Long-term exposure also induced resistance to hypoxia-induced apoptosis.

Conclusions:

  • Loss of VEGF signaling in cancer cells, induced by VEGF-R inhibitors like regorafenib, may promote acquired therapy resistance.
  • This resistance is characterized by the gain of malignant phenotypes, including apoptosis resistance and enhanced migration/invasion.
  • These findings highlight a potential mechanism for tumor progression and treatment failure in colorectal cancer.

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