Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway

Abstract

Objectives Hepatocellular carcinoma (HCC) still presents a high incidence of malignant tumours with poor prognosis. There is an urgent need for new therapeutic agents with high specificity, low toxicity and favourable solubility for the clinical treatment of HCC. Materials and Methods The bioactivity of human umbilical cord serum was investigated by proteomics biotechnology and a primitive peptide with certain biological activity was identified. The antitumour effect of RR‐171 was detected by cell viability assay in vitro, and determined by subcutaneous xenograft models assay and miniPDX assay in vivo. Pull‐down experiments were conducted to identify the potential targeting proteins of RR‐171. Immunofluorescence assay and tubulin polymerization assay were conducted to explore the relationship between RR‐171 and α‐tubulin. Fluorescence imaging in xenograft models was used to explore the biodistribution of RR‐171 in vivo. A phosphospecific protein microarray was performed to uncover the underlying signalling pathway by which RR‐171 induces tumour cell death. Results The results indicated that RR‐171 could be effective in the treatment of HCC in vivo and in vitro. RR‐171 could aggregate significantly in solid tumours and had no obvious systemic toxicity in vivo. RR‐171 could interact with α‐tubulin and activate the NF‐Kappa B pathway in HCC cells. Conclusions Taken together, RR‐171 exhibited significant antitumour activity against HCC in vivo and in vitro and could potentially be used in the clinical application of HCC.

Prediction of CAF-related genes in immunotherapy and drug sensitivity in hepatocellular carcinoma: a multi-database analysis

“…Signaling enrichment analysis of these associated genes showed that they were enriched in the “AGE-RAGE signaling pathway in diabetic complications” and the “NF-kappa B signaling pathway”. Consistently, several studies showed that these signaling pathways are significantly involved in the development of HCC [ 45 – 49 ], which further confirms that CAFs may indirectly influence the development of HCC through these CAF-related genes.…”