Abstract

Molecular imaging enables non-invasive monitoring of tumor growth, progression, and drug treatment response, and it has become an important tool to promote biological studies in recent years. In this study, we comprehensively evaluated the in vivo anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer based on the optical molecular imaging systems including micro-computer tomography (Micro-CT), bioluminescence molecular imaging (BLI) and fluorescence molecular tomography (FMT). Firefly luciferase (fLuc) and green fluorescent protein (GFP) dual labeled human hepatocellular carcinoma cells (HCC-LM3-fLuc-GFP cells) were used to establish the subcutaneous and orthotopic liver tumor model. After the tumor cells were implanted 14∼18 days, Endostar (5 mg/kg/day) was administered through an intravenous tail vein injection for continuous 14 days. The computer tomography angiography (CTA) and BLI were carried out for the subcutaneous tumor model. FMT was executed for the orthotopic tumor model. The CTA data showed that tumor vessel formation and the peritumoral vasculature of subcutaneous tumor in the Endostar treatment group was significantly inhibited compared to the control group. The BLI data exhibited the obvious tumor inhibition day 8 post-treatment. The FMT detected the tumor suppression effects of Endostar as early as day 4 post-treatment and measured the tumor location. The above data confirmed the effects of Endostar on anti-angiogenesis and tumor suppression on liver cancer. Our system combined CTA, BLI, and FMT to offer more comprehensive information about the effects of Endostar on the suppression of vessel and tumor formation. Optical molecular imaging system enabled the non-invasive and reliable assessment of anti-tumor drug efficacy on liver cancer.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common cancer in the world and is responsible for more than 600,000 deaths annually [1]

  • Angiogenesis is required for invasive tumor growth and metastasis, so it plays an important role in the control of cancer progression [4,5]

  • HCC tumors depend on a rich blood supply [6,7], inhibition of angiogenesis has constituted a crucial point in liver cancer therapy

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancer in the world and is responsible for more than 600,000 deaths annually [1]. The disease is often detected at a late stage, when potentially curative therapies are often ineffective [2]. Most cancer patients show disease recurrence that rapidly progresses to the advanced stages with vascular invasion and their 5-year relative survival rate is only 7% [3]. New therapies and new detection methods for this aggressive disease are extremely needed. Angiogenesis is required for invasive tumor growth and metastasis, so it plays an important role in the control of cancer progression [4,5]. The rapid growth of the tumor needs a large amount of nutrients and oxygen, which prompted the growth of blood vessels. HCC tumors depend on a rich blood supply [6,7], inhibition of angiogenesis has constituted a crucial point in liver cancer therapy

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