Adenovirus armed with VGLL4 selectively kills hepatocellular carcinoma with G2/M phase arrest and apoptosis promotion

Area of Science:

• Oncology
• Molecular Biology
• Gene Therapy

Background:

• Vestigial-Like Family Member 4 (VGLL4) is a known inhibitor of cell proliferation and tumor growth.
• Hepatocellular carcinoma (HCC) is a prevalent cancer with significant mortality.
• Targeted gene therapy offers a promising avenue for HCC treatment.

Purpose of the Study:

• To investigate the role of VGLL4 in hepatocellular carcinoma (HCC) progression.
• To develop and evaluate a novel oncolytic adenovirus (Ad-sp-VGLL4) engineered to deliver the VGLL4 gene.
• To assess the therapeutic potential of Ad-sp-VGLL4 against HCC in vitro and in vivo.

Main Methods:

• Investigated VGLL4's effect on HCC cell cycle, identifying G2/M phase arrest.
• Constructed a survivin-regulated oncolytic adenovirus (Ad-sp-VGLL4) carrying the VGLL4 gene.
• Evaluated Ad-sp-VGLL4's targeting selectivity, antitumor activity, and apoptosis induction in HCC cells and xenograft models.

Main Results:

• VGLL4 induces G2/M phase arrest in HCC cells.
• Ad-sp-VGLL4 demonstrated high selectivity for HCC cells with minimal toxicity to normal cells.
• The engineered adenovirus enhanced antitumor activity by promoting G2/M phase arrest and apoptosis.
• Ad-sp-VGLL4 suppressed transplanted HCC tumor growth in vivo.

Conclusions:

• Ad-sp-VGLL4 exhibits significant antitumor capacity against HCC.
• The novel oncolytic adenovirus holds great potential for HCC therapy.
• Targeted delivery of VGLL4 via Ad-sp-VGLL4 represents a promising strategy for hepatocellular carcinoma treatment.