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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Anlotinib Suppresses Colorectal Cancer Proliferation and Angiogenesis via Inhibition of AKT/ERK Signaling Cascade

Qian Yang1, Laichao Ni1, Saber Imani1

  • 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China.

Cancer Management and Research
|July 2, 2020
PubMed
Abstract

Insights

Anlotinib effectively inhibits colorectal cancer (CRC) growth by suppressing cell proliferation and angiogenesis. This multi-target tyrosine kinase inhibitor shows promise as a novel therapeutic strategy for CRC treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Anlotinib is a potent multi-target tyrosine kinase inhibitor with known anti-tumor activity.
  • Its specific effects and mechanisms in colorectal cancer (CRC) require further elucidation.

Purpose of the Study:

  • To investigate the anti-tumor effects of anlotinib in colorectal cancer.
  • To elucidate the underlying molecular mechanisms of anlotinib's action in CRC pathogenesis.

Main Methods:

  • In vitro studies utilized MTT, tube formation, wound healing, and transwell assays to assess proliferation, migration, invasion, and angiogenesis.
  • Flow cytometry analyzed cell cycle and apoptosis.
  • In vivo studies involved a CRC xenograft mouse model, with immunohistochemistry and Western blot evaluating protein expression (Ki-67, CD31) and signaling pathways (VEGFR-2/AKT, FGFR, PDGFRβ, ERK).

Main Results:

  • Anlotinib dose-dependently inhibited CT26 cell proliferation, migration, invasion, and human umbilical vein endothelial cell (HUVEC) tube formation.
  • Significant induction of apoptosis and G2/M cell cycle arrest was observed.
  • In vivo, anlotinib suppressed tumor growth, prolonged survival, downregulated CD31 and Ki-67, and inhibited VEGFR-2/AKT, FGFR, PDGFRβ, and ERK signaling.

Conclusions:

  • Anlotinib demonstrates significant anti-proliferative and anti-angiogenic effects in colorectal cancer models.
  • These effects are mediated through the inhibition of the AKT/ERK signaling pathway.
  • Anlotinib represents a potential novel therapeutic strategy for colorectal cancer treatment.
Keywords:
angiogenesisanlotinibcolorectal cancerproliferationtyrosine kinase inhibitor

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