Reference Detail

Ref Type Journal Article
PMID (27633584)
Authors Yassin S, Hu J, Xu H, Li C, Setrerrahmane S
Title In vitro and in vivo activities of an antitumor peptide HM-3: A special dose-efficacy relationship on an HCT‑116 xenograft model in nude mice.
Journal Oncology reports
Vol 36
Issue 5
Date 2016 Nov
URL
Abstract Text Anti-angiogenesis is an important therapy for cancer treatment. Peptide HM-3 is an integrin antagonist with anti-angiogenic and antitumor activity. Previous research found that HM-3 at an effective dose inhibited tumor growth whereas at higher doses, the inhibitory effect gradually decreased. In the present study, three human tumor cell lines, human colorectal cancer cell (HCT-116) and human hepatic cancer cell (Hep G-2 and SMMC-7721), were selected and their interactions with HM-3 were compared with western blot and flow cytometric assays. The effect of HM-3 on the migration of two tumor cell lines (HCT-116 and Hep G-2) was also evaluated and a bell-shaped dose-efficacy curve was found for both cell lines. Furthermore, in vivo imaging in BALB/c nude mice confirmed that HM-3 had a short half-life and targeted the tumor tissue. Moreover, on an HCT-116 xenograft model in BALB/c nude mice, HM-3 at 3 mg/kg inhibited tumor growth with an inhibition rate of 71.5% (by tumor mass) whereas at 12 and 48 mg/kg, the inhibition rates were 59.2 and 36.0%, respectively. Immunohistochemistry analyses found that both sunitinib (60 mg/kg) and HM-3 (3 and 48 mg/kg) decreased microvascular density and increased percent of HIF-1α and VEGF expressing cells. The present study investigated the effect of tumor microenvironments on the antitumor effect of HM-3 and concluded that HM-3 inhibited angiogenesis and thereafter tumor growth by directly inhibiting HUVEC migration. The special dose-efficacy curves for antitumor effect and for cell migration inhibition were correlated. The present study also confirmed that the effective dose has to be strictly defined for better clinical applications of anti‑angiogenic drugs such as HM-3.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
HM-3 HM-3 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
HM-3 HM-3 is a synthetic peptide derived from endostatin, which targets integrin alpha v beta 3, possibly resulting in inhibition of angiogenesis and tumor growth (PMID: 27633584).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown colon cancer not applicable HM-3 Preclinical - Cell line xenograft Actionable In a preclinical study, a colon cancer cells treated with HM-3 demonstrated reduced cell migration in culture and inhibition of tumor growth in xenograft models (PMID: 27633584). 27633584