Abstract

Hedyotis diffusa (HD) plus Scutellaria barbata (SB) have been widely used in antitumor clinical prescribes as one of herb pairs in China. We investigated the effect of aqueous extract from Hedyotis diffusa plus Scutellaria barbata at the equal weight ratio (HDSB11) in inhibiting the growth of murine non-small-cell lung cancer cell (NSCLC) line LLC in vivo and in vitro in this study. Compared with other aqueous extracts, HDSB11 showed the lowest IC50 in inhibiting cell proliferation at 0.43 mg/ml. Besides, HDSB11 effectively suppressed colony formation and induced cell apoptosis. The further assessment of HDSB11 on the murine Lewis-lung-carcinoma-bearing mouse model showed it significantly inhibited tumors' bioluminescence at the dose of 30 g crude drug/kg. Mechanistically, HDSB11 attenuated the expressions of NLRP3, procaspase-1, caspase-1, PRAP, Bcl-2, and cyclin D1 and downregulated the phosphorylation levels of NF-κB, ERK, JNK, and p38 MAPK. In conclusion, HDSB11 could alleviate cell proliferation and colony formation and induce apoptosis in vitro and tumor growth in vivo, partly via NF-κB and MAPK signaling pathways to suppress NLRP3 expression.

Highlights

  • Lung cancer is one of the most common cancers worldwide, according to the latest global cancer report released by the World Health Organization [1]

  • Modern pharmacological studies confirmed that HD and Scutellaria barbata D. Don (SB) could inhibit tumor cell proliferation, enhance the body’s immunity, induce tumor cell apoptosis, and reverse drug resistance [12,13,14,15,16,17,18]. e clinical drug database analysis showed that Hedyotis diffusa Willd plus Scutellaria barbata D

  • Dulbecco’s Modified Eagle Medium (DMEM), RPMI-1640, Fetal Bovine Serum (FBS), and 0.25% trypsin were obtained from Gibco (California, USA). hygromycin B, MTT, crystal violet powder, and DMSO were purchased from Sigma (California, USA). e apoptosis detection kit was purchased from BD (State of New Jersey, USA)

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Summary

Introduction

Lung cancer is one of the most common cancers worldwide, according to the latest global cancer report released by the World Health Organization [1]. E available options for NSCLC treatments are physical surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, and a combination of these abovementioned therapies [3, 4]. Pathogen-associated molecular patterns (PAMPs) or risk-associated molecular patterns (DAMPs) induce expressions of inflammasome components NLRP3, pro-IL-1β, and pro-IL-18. Increasing evidence indicates the NLRP3 inflammasome plays a vital role in the occurrence and development of various tumors, including lung cancer, breast cancer, endometrial cancer, and melanoma [7,8,9,10,11]. Hedyotis diffusa Willd (HD) and Scutellaria barbata D. E clinical drug database analysis showed that Hedyotis diffusa Willd plus Scutellaria barbata D.

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