Combination of interferon-gamma and autophagy inhibitor as a therapeutic approach in oral squamous cell carcinoma

Abstract

Background: Former clinical trials and experimental research have indicated that interferon-gamma (IFNγ) therapy does not achieve an ideal effect in solid tumors. Autophagy has been associated with tumor chemoresistance. The aim of this study was to explore the efficacy of IFNγ and autophagy inhibitor in the combination treatment of oral squamous cell carcinoma (OSCC). Method: IFNγ-induced apoptosis was evaluated by the expression of relative proteins (cleaved-PARP and caspase-3) and flow cytometry. IFNγ-induced autophagy was assessed by the expression of Beclin1, LC3B, and P62. The synergistic effect of IFNγ and autophagy inhibitor (chloroquine) was evaluated in vitro and in vivo.Findings: IFNγ induced anti-proliferation, apoptosis, and autophagy in OSCC cells. Autophagy-related protein 5 (ATG5) was a key feature in IFNγ-induced autophagy flux. IFNγ and chloroquine had obvious synergistic effects on cellular growth inhibition and apoptosis promotion in OSCC cells and xenograft models. Interpretation: Our findings suggest that IFNγ-induced autophagy plays a cellular protective role, and blocking autophagy flux can promote IFNγ-mediated OSCC cell apoptosis. The combination of IFNγ and autophagy inhibitors represents a novel strategy for OSCC therapy.

Alphavirus-driven Interferon Gamma (IFNg) Expression Inhibits Tumour Growth in Orthotopic 4T1 Breast Cancer Model

“…), which correlated with clinical observations [22]. A promising way to enhance the antitumour effects of IFNg along with the inhibition of its potential protumour effects is shown to be a complex treatment with immune checkpoint inhibitors [23][24][25], chemoimmunotherapy [26,27] alone or in combination with oncolytic viral vectors additionally inducing the innate immunity in tumours [28,29].…”

Stimulator of interferon response cGAMP interactor overcomes ERBB2-mediated apatinib resistance in head and neck squamous cell carcinoma

“…Therapeutic strategies targeting vascular endothelial growth factor receptors (VEGFRs) have been studied extensively because of the important roles of VEGFRs in carcinogenesis [ 17 ]. Apatinib is an oral tyrosine kinase inhibitor of VEGFR-2 that can induce autophagy [ 18 ] and apoptosis, and suppresses tumor proliferation in anaplastic thyroid cancer [ 8 ], hepatocellular carcinoma [ 19 ], and osteosarcoma [ 20 ]. However, effective treatment is challenged by apatinib resistance [ 21 ].…”

miR-30a-5p suppresses lung squamous cell carcinoma via ATG5 - mediated autophagy

“…Complete medium was used for cell culture. All cells line were then nurtured according to former relative research [ 15 ].…”

“…Comply with manufacturer instruction, Axygen RNA Miniprep Kit (Axygen, USA) was used to obtain total RNA. The following process were performed according to former relative research [ 15 ]. The human primer sets used were as follows: GAPDH forward: 5′-CCTCTGACTTCAACAGCGAC-3′ and reverse: 5′-TCCTCTTGTGCTCTTGCTGGC-3′; ATG5 forward: 5′-TGCAGATGGACAGTTGCACA-3′ and reverse: 5′-CCACTGCAGAGGTGTTTCCA-3′.…”

“…Yang et al [ 13 ] revealed that autophagy induces tumor growth by alternating p53. According to former research relating to oral squamous cell carcinoma, autophagy was considered to play a key role in either nurturing cancer cells [ 13 ] or regulating cell apoptosis [ 14 , 15 ].…”