SH003 Inhibits Proliferation and Induces Apoptosis in NSCLC Cell Lines by Inhibiting the Receptor Tyrosine Kinase-related Pathway

Abstract

Background/aim: SH003, a novel herbal mixture consisting of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, has shown promising anti-cancer effects in various cancers, including non-small cell lung cancer (NSCLC), which comprises approximately 85% of all lung cancer cases. Characterized by high mortality rates due to late-stage diagnosis and frequent development of resistance to traditional therapies, NSCLC is a significant clinical challenge. This study investigated the anti-cancer effects of SH003 on NSCLC cells, focusing on its role in modulating receptor tyrosine kinase (RTK) signaling pathways.

Materials and methods: NSCLC cell lines (A549, H460, HCC827) were treated with SH003 to evaluate cell viability (MTT assay), colony formation, apoptosis (Annexin V/7-AAD staining, western blot), and cell cycle distribution (PI staining). Phosphorylation of RTKs and related signaling molecules was analyzed using a phospho-RTK array and western blot. In vivo anti-tumor effects were assessed using an A549 xenograft mouse model treated orally with SH003.

Results: NSCLC cell lines A549, H460, and HCC827 treated with SH003 showed significant, dose-dependent cell viability and colony formation reductions. SH003 induced apoptosis, evidenced by increased cleaved PARP and caspase-8 levels, and caused G₁/S cell cycle arrest. Additionally, SH003 treatment decreased phosphorylation of multiple receptor tyrosine kinases (RTKs), including ErbB4, FGFR1, FGFR3, and PDGFRβ, as confirmed by an RTK array. In an A549 xenograft mouse model, SH003 inhibited tumor growth without affecting body weight, indicating low systemic toxicity.

Conclusion: SH003 is a promising multi-target therapeutic agent for NSCLC, offering a novel strategy to improve patient outcomes.

Keywords: NSCLC; SH003; apoptosis; receptor tyrosine kinase.