Panax notoginseng Saponins Enhance Chemotherapy Carboplatin and Immune Checkpoint Blockades PD1ab by Modulating SERPINE1 Downregulation in LUAD

Abstract

Introduction and Objectives Panax notoginseng saponins (PNS), extracted from Chinese ginseng, exert various pharmacological activities, including anti-tumor effects. Lung cancer remains the malignancy with the highest morbidity and mortality rates. However, the mechanisms underlying PNS’s potential tumor-inhibitory effects on lung adenocarcinoma (LUAD) remain largely unknown and warrant investigation. Purpose This study aimed to explore the PNS’s potential tumor-inhibitory effects and related mechanisms in LUAD. Materials and Methods LUAD cell lines A549 and Lewis were utilized to examine the proliferation, colony formation, and migration of LUAD cells after PNS treatment. WI38 cells were employed to evaluate the toxic impact of PNS on human lung fibroblasts. A Lewis subcutaneous tumor-bearing model was established to assess the combined effects of PNS and carboplatin (CBP) or immune checkpoint blockade with programmed cell death 1 antibody (PD1ab). Lentivirus transfection and quantitative polymerase chain reaction (qPCR) assays were conducted to explore the role of serine protease inhibitor clade E member 1 (SERPINE1) in PNS’s anti-tumor mechanism. Immunohistochemistry was utilized to detect CD8 + T cell infiltration in tumor tissue. Cell counting kit-8 and qPCR assays were applied to determine the specific PNS components exerting anti-tumor effects. Results In vitro and in vivo results indicated that PNS selectively inhibited the proliferation, colony formation, and migration of LUAD cells while promoting CD8 + T-cell infiltration in tumor tissue. Consequently, PNS enhanced the inhibitory effects of CBP and PD1ab on LUAD tumors. Mechanistically, the results preliminarily indicated that PNS might impede tumor progression and enhance CBP and PD1ab effects by downregulating SERPINE1. Five PNS components, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Rd, ginsenoside Re, and ginsenoside Rb1, demonstrated anti-tumor effects. Conclusion PNS suppressed LUAD progression and enhanced CBP and PD1ab therapeutic effects by downregulating SERPINE1 expression, indicating its potential as a promising agent for LUAD therapy.