Live Biotherapeutics Drug Discovery Services for Hepatocellular Carcinoma (HCC)

Recent experimental and clinical studies have revealed that the alteration of gut-liver axis plays a pivotal role in hepatocellular carcinoma (HCC). Altered gut microbiota and endotoxemia are increasingly recognized as critical components in promoting the progression of chronic liver diseases to HCC. Probiotics have been suggested as a novel, safe, and cost-effective approach for the prevention or treatment of HCC.

With our state-of-the-art technology and industry-leading expertise in the development of next-generation probiotics (NGPs), Creative Biolabs performs probiotics identification for single strains and blends. We support your drug development with NGP strain identification, genomic analysis, and test your NGPs for stability along the way. Our scientists are more than happy to share our knowledge and passion in this field to facilitate help our clients’ research in the prevention and treatment of HCC.

Introduction of HCC

HCC, the most common primary liver cancer, is a leading cause of death worldwide and one of the dreaded complications of chronic liver disease. Eighty to ninety percent of all cases of HCC are linked to cirrhosis or fibrosis, and the well-recognized risk factors are infections with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic cirrhosis, as well as hemochromatosis. Nowadays, the main treatment options for HCC include surgical resection, liver transplantation, radiofrequency ablation (RFA) and trans-arterial chemoembolization, radioembolization, and emerging systemic chemotherapeutic and targeted agents such as sorafenib, but despite the significant improvements in medical management the prognosis of patients with advanced HCC is still poor. Therefore, HCC is undoubtedly a disease for which there is an urgent need for the development of alternative therapies.

Proposed mechanism of action of probiotics against HCC. Fig.1 Proposed mechanism of action of probiotics against HCC. (Wan, 2018)

HCC and Probiotics

Probiotic therapy as a safe, inexpensive, and noninvasive strategy can reduce pathophysiological symptoms and improve liver disease including HCC without side effects. Mechanisms by which probiotics exert their anti-cancer effects include their ability to bind carcinogens, modulation of gut microbiota, improvement of intestinal barrier function, and immunomodulation. There are few studies regarding the use of probiotic supplements as a dietary approach to reduce the risk of HCC.

  • In a clinical study, dietary supplementation using probiotics such as viable Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii subsp. Shermani) could effectively reduce the excretion of aflatoxin-DNA adduct (AFB1-N7-guanine) in urine.
  • In a rat study, investigating the chemopreventive effect of probiotic-fermented milk and chlorophyllin on AFB1-induced HCC, the probiotics treatment reduced the tumor incidence, which suggests the protective capacity of probiotics against AFB1-induced hepatocarcinogenesis. In another rat study, administration of VSL#3 (containing Lactobacillus spp, Bifidobacterium spp., and Streptococcus spp.) mitigated DEN-induced hepatocarcinogenesis, and thus inhibiting the progression of cirrhosis to HCC.
  • Another study has reported that probiotics inhibit HCC progression in mice. Feeding the probiotics mixture Prohep (containing Lactobacillus rhamnosus GG, Escherichia coli, and heat-inactivated VSL#3) to tumor-injected mice could shift the gut microbiota composition and reduce the size of liver tumors. In addition to the reduction of tumor size, angiogenic factors were down-regulated by probiotics administration.

NGPs Discovery Service at Creative Biolabs

The presence of high levels of lipopolysaccharide (LPS) and bacteria in the blood results in portal hypertension and ensuing hepatocyte damage. Several strategies including the usage of antibiotics, prebiotics, and probiotics can be used to prevent the overgrowth of pathogens. Compared to prebiotic and antibiotic therapy, probiotics strains are safer and less expensive therapy. Equipped with world-leading technology platforms and professional scientific staff in live biotherapeutics drug discovery, Creative Biolabs has pioneered the discovery of novel NGPs. Our comprehensive services include but are not limited to new NGP identification, characterization, analyses & qualification, and good manufacturing practice (GMP) scale-up.

Creative Biolabs offers accurate and effective solutions for researchers who are committed to developing NGPs for the prevention and treatment of HCC. We are pleased to use our extensive experience and advanced platform to offer the best service to satisfy each demand from our customers. Please contact us for more information and a detailed quote.

Reference

  1. Wan, M.L.; El-Nezami, H. Targeting gut microbiota in hepatocellular carcinoma: probiotics as a novel therapy. Hepatobiliary surgery and nutrition. 2018, 7(1): 11.

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