Recombinant virus expressing hIFN-λ1 (rL-hIFN-λ1) has important effects on endoplasmic reticulum stress, autophagy and apoptosis in small cell lung cancer.

Background: Small cell lung cancer (SCLC) is an aggressive tumor with a poor prognosis. Human IFN-λ1 (IL-29), belonging to the type III IFN family, captured increasing attention recently due to its crucial role in developing tumors. Recent studies have revealed that the recombinant Newcastle Disease Virus (NDV) expressing human IFN-λ1 (rL-hIFN-λ1) plays a critical role in the development of tumors. However, the role of rL-hIFN-λ1 in SCLC is still unknown.

Methods: We determined the concentration of the virus intervention, followed by successfully infection in virus. We also investigated the effects of rL-hIFN-λ1 on endoplasmic reticulum stress (ERS), apoptosis and autophagy in H446 cells, and explored the interaction among the three.

Results: We found that the ERS, autophagy and apoptosis related proteins were significantly upregulated after infected with rL-hIFN-λ1 or NDV. In addition, both 4-phenylbutyric acid (4-PBA) or 3-Methyladenine (3-MA) could downregulate the expression of related proteins which increased by rL-hIFN-λ1. Furthermore, we found that both B-cell lymphoma-2 (BCL-2) knockdown or Rapamycin (Rapa) could increase ERS, autophagy and apoptosis.

Conclusions: Our findings suggest that rL-hIFN-λ1 can induce ERS, autophagy and apoptosis in SCLC H446 cells, particularly, autophagy plays an important role during this process. Furthermore, rL-hIFN-λ1 might provide a potential biological treatment target for lung cancer treatment.