IPS-1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus

Quan Zhang1, Xiaoshuang Xu, Yan Yuan

  • 1Comparative Medicine Center, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Insights

Inactivated Sendai virus (HVJ-E) triggers apoptosis in melanoma cells via caspase and MAPK pathways. Intratumoral HVJ-E treatment showed direct oncolytic effects in mice.

Area of Science:

  • Oncology
  • Virology
  • Cell Biology

Background:

  • Inactivated Sendai virus (HVJ-E) induces apoptosis in cancer cells via JAK/STAT pathways.
  • The precise molecular mechanisms of HVJ-E-induced apoptosis involving other signaling pathways are not fully understood.

Purpose of the Study:

  • To investigate the signaling pathways mediating apoptosis induced by HVJ-E in murine B16F10 melanoma cells.
  • To elucidate the role of intrinsic apoptotic pathways and MAPK signaling in HVJ-E's oncolytic mechanism.

Main Methods:

  • Treatment of B16F10 melanoma cells with HVJ-E.
  • Analysis of apoptosis induction via caspase and MAPK pathways.
  • Assessment of the involvement of IFN-β promoter stimulator-1 (IPS-1) and type I interferon (IFN).
  • In vivo studies using a murine melanoma model (BALB/c nude mice).

Main Results:

  • HVJ-E induced apoptosis in B16F10 cells through the caspase pathway, specifically involving caspase-9 (intrinsic apoptosis).
  • Mitogen-activated protein kinase (MAPK) pathway activation also contributed to HVJ-E-induced apoptosis.
  • Caspase pathway activation was dependent on IPS-1 and type I IFN, while MAPK activation was IPS-1 dependent but type I IFN independent.
  • Intratumoral HVJ-E administration demonstrated direct oncolytic activity in a mouse melanoma model.

Conclusions:

  • HVJ-E induces melanoma cell apoptosis via both intrinsic caspase-dependent and MAPK-dependent pathways.
  • The study reveals distinct dependencies on IPS-1 and type I IFN for these pathways.
  • HVJ-E exhibits direct oncolytic potential, offering insights into its therapeutic application for melanoma.

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