IL-12 induces autophagy in human breast cancer cells through AMPK and the PI3K/Akt pathway

Abstract

Interleukin-12 (IL-12) serves an important role in immune responses and antitumor activity. The study of the association between autophagy and cancer cells remains controversial. The present study aimed to investigate the effect of IL‑12 on autophagy in the human breast cancer cell lines MDA‑MB‑231 and MCF‑7, and the possible molecular mechanism. Breast cancer cells were treated with different concentrations of recombinant IL‑12. The expression of the autophagy-associated protein microtubule‑associated protein light chain 3 (LC3) was determined using western blot analysis, fluorescein isothiocyanate‑labeled LC3 was detected using fluorescence microscopy and autophagosomes were examined using transmission electron microscopy. Alterations in the phosphatidylinositol 3‑kinase/Rac‑α serine/threonine protein kinase (PI3K/Akt) and 5'‑AMP‑activated protein kinase subunit β‑1 (AMPK) pathways, in addition to pathway‑associated proteins, were detected using western blotting, following treatment with IL‑12 and pretreatment with the PI3K/Akt activator insulin‑like growth factor or the AMPK inhibitor compound C. It was observed that IL‑12 was able to upregulate the expression of the autophagy‑associated protein LC3 in a concentration‑ and time‑dependent manner, and induce the formation of autophagosomes in the two cell lines, and that the above effects involved the inhibition of the PI3K/Akt signaling pathway and the activation of the AMPK signaling pathway.

Identification of microRNA expression in sentinel lymph nodes from patients with breast cancer via RNA sequencing for diagnostic accuracy

“…For example, the blockade of PI3K–Akt by Slit2, which is secreted by stromal fibroblasts, significantly restrained breast cancer cell proliferation . Induction by interleukin‐12 and PI3K–Akt can activate autophagy and contribute to tumorigenesis, whereas mutations in the PI3K–Akt/mammalian target of rapamycin signaling pathway are frequently observed and are associated with a poor prognosis of breast cancer …”

“…The qRT-PCR results showed that miR-200a-3p, miR-200a-3p and Slit2, which is secreted by stromal fibroblasts, significantly restrained breast cancer cell proliferation. 23 Induction by interleukin-12 and PI3K-Akt can activate autophagy and contribute to tumorigenesis, 24 whereas mutations in the PI3K-Akt/mammalian target of rapamycin signaling pathway are frequently observed and are associated with a poor prognosis of breast cancer. 24 In the present study, we constructed an miRNA-mRNA interaction network to obtain an overview of the putative function of the most differentially expressed miRNAs.…”

“…23 Induction by interleukin-12 and PI3K-Akt can activate autophagy and contribute to tumorigenesis, 24 whereas mutations in the PI3K-Akt/mammalian target of rapamycin signaling pathway are frequently observed and are associated with a poor prognosis of breast cancer. 24 In the present study, we constructed an miRNA-mRNA interaction network to obtain an overview of the putative function of the most differentially expressed miRNAs. This miRNA-mRNA interaction network suggested that differentially expressed miRNAs regulate tumor growth and metastasis-related genes such as EGFR, 25,26 MET, 27 SOX9, 28 SP1, PTEN, 29 FOXO1 30 and ZEB1.…”

Transcription repressor protein ZBTB25 interacts with HDAC1 in macrophages infected withMycobacterium tuberculosis,and its inhibition leads to autophagy and killing of the intracellular pathogen

“…Interestingly Jung et al (2014) showed that IL-12 is involved in antimicrobial action by activating the fusion of phagosome and lysosome via IFN-γ. Although IL-12-induced autophagy has been reported in breast cancer cells, human macrophages, and lung epithelial cells (Lin et al, 2017;Yang et al, 2018), the precise function of IL-12 in inducing this process…”

Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages

“…However, the possible mechanism by which HO-1/CO exerted a cytoprotective effect has not completely elucidated. In addition, as a major survival signaling pathway, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) resulted in the nuclear translocation of NF-E2 related factor 2 (Nrf2) and subsequently increased the expression of the downstream target gene, HO-1 (14,15). Additionally, phosphorylation of Akt at Ser473 via a PI3K-dependent pathway served a crucial role in regulating mitochondrial oxidative stress-mediated tissue injury (16,17).…”