The Role of Serine Protease 8 in Mediating Gefitinib Resistance in Non-small Cell Lung Cancer


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Abstract

Objective:This investigation aims to explore the expression levels of serine protease 8 (PRSS8) in gefitinib-resistant Non-Small Cell Lung Cancer (NSCLC) cell lines (PC9/GR) and elucidate its mechanism of action.

Methods:We measured PRSS8 expression in gefitinib-resistant (PC9/GR) and sensitive (PC9) NSCLC cell lines using Western blot analysis. PRSS8-specific small interfering RNA (PRSS8-siRNA), a recombinant plasmid, and a corresponding blank control were transfected into PC9/GR cells. Subsequently, Western blot analyses were conducted to assess the expression levels of PRSS8, phosphorylated AKT (p-AKT), AKT, phosphorylated mTOR (p-mTOR), mTOR, and various apoptosis-related proteins within each group. Additionally, a cell proliferation assay utilizing Cell Counting Kit-8 (CCK8) was performed on each group treated with gefitinib.

Results:PRSS8 expression was markedly higher in PC9/GR cells compared to PC9 cells (p < 0.05). The group treated with PRSS8-siRNA exhibited significantly reduced protein expression levels of PRSS8, p-AKT, p-mTOR, β-catenin, and BCL-2 compared to the control siRNA (Con-siRNA) group, whereas expressions of Caspase9 and Bax were significantly increased. In the untransfected PC9/GR cells, protein expressions of PRSS8, p-AKT, pmTOR, and BCL-2 were significantly elevated when compared with the plasmid-transfected group, which also showed a significant reduction in Bax expression. The proliferative activity of the PRSS8-siRNA group postgefitinib treatment was significantly diminished at 24, 48, and 72 hours in comparison to the Con-siRNA group.

Conclusion:The findings indicate that PRSS8 contributes to the acquisition of resistance to gefitinib in NSCLC, potentially through regulation of the AKT/mTOR signaling pathway.

About the authors

Hai-Jing Gao

Department of Clinical Laboratory, The Affiliated Hospital of Chende Medical University

Email: info@benthamscience.net

Xue-Li Geng

Department of Clinical Laboratory, The Affiliated Hospital of Chende Medical University

Author for correspondence.
Email: info@benthamscience.net

Ling-Ling Wang

Department of Clinical Laboratory, The Affiliated Hospital of Chende Medical University

Email: info@benthamscience.net

Chun-Nan Zhao

Department of Clinical Laboratory, The Affiliated Hospital of Chende Medical University

Email: info@benthamscience.net

Zong-Ying Liang

Department of Thoracic Surgery, The Affiliated Hospital of Chende Medical University

Email: info@benthamscience.net

En-Hong Xing

Department of Central Laboratory, The Affiliated Hospital of Chende Medical University

Email: info@benthamscience.net

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