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Effects of Oncolytic Vaccinia Viruses Harboring Different Marine Lectins on Hepatocellular Carcinoma Cells

Yanrong Zhou1, Qianpeng Wang1, Qi Ying1

  • 1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

International Journal of Molecular Sciences
|February 25, 2023
PubMed

Insights

Oncolytic vaccinia viruses (oncoVV) armed with marine lectins show varied effectiveness against hepatocellular carcinoma (HCC) cell lines. Oncolytic vaccinia virus-Aphrocallistes vastus lectin (oncoVV-AVL) demonstrated the strongest cytotoxicity, with mechanisms varying by cell type.

Area of Science:

  • Oncology
  • Virology
  • Biotechnology

Background:

  • Oncolytic viruses represent a promising frontier in cancer therapeutics.
  • Previous research indicated that vaccinia viruses engineered with marine lectins enhance antitumor activity across various cancers.

Purpose of the Study:

  • To evaluate the cytotoxic effects of oncolytic vaccinia viruses (oncoVV) engineered with four distinct marine lectins on hepatocellular carcinoma (HCC) cells.
  • To investigate the underlying mechanisms of oncoVV-lectin cytotoxicity and replication in different HCC cell lines.

Main Methods:

  • Generation of oncolytic vaccinia viruses (oncoVV) harboring Tachypleus tridentatus lectin (oncoVV-TTL), Aphrocallistes vastus lectin (oncoVV-AVL), white-spotted charr lectin (oncoVV-WCL), and Asterina pectinifera lectin (oncoVV-APL).
  • Assessment of the cytotoxic effects of these recombinant viruses on Hep-3B, Huh7, and PLC/PRF/5 HCC cell lines.
  • Analysis of cell-type-dependent mechanisms, including apoptosis, viral replication, and associated signaling pathways (e.g., MAPK, Hippo, PI3K, AMPK, lipid metabolism, androgen pathways).

Main Results:

  • OncoVV-AVL exhibited the highest cytotoxicity against Hep-3B cells, followed by oncoVV-APL, oncoVV-TTL, and oncoVV-WCL.
  • Huh7 cells were sensitive to oncoVV-TTL and oncoVV-WCL, while PLC/PRF/5 cells responded to oncoVV-AVL and oncoVV-TTL.
  • The cytotoxicity and replication of oncoVV-lectins were found to be cell-type-dependent, involving complex interactions with pathways like AMPK, Hippo, PI3K, MAPK, lipid metabolism, and androgen signaling.

Conclusions:

  • Oncolytic vaccinia viruses armed with specific marine lectins, particularly oncoVV-AVL, show potential as a therapeutic strategy for hepatocellular carcinoma.
  • The efficacy and underlying mechanisms of these oncolytic viruses are highly dependent on the specific HCC cell type and the lectin employed.
  • Further research into the intricate signaling pathways modulated by these oncoVV-lectins could pave the way for optimized cancer therapies.
Keywords:
apoptosismarine lectinsoncolytic vaccinia virussignaling pathwaysviral replication

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