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
Authors: Hanmei Xu
Sarra Setrerrahmane
Sitelbanat Yassin
Jialiang Hu
Ce Li
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Anti-angiogenesis; Peptide HM-3; Tumor growth inhibition; Human tumor cell lines; Migration inhibition
Affiliations: The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 In Figure 7, microscopy data has been duplicated (HM-3 3mg vs HM-3 48 mg). ![file] , 
 #1 [Corrigendum] https: www.spandidos-publications.com 10.3892 or.2020.7503 Oncol Rep 36: [Related article:] 2951-2959, 2016; DOI: 10.3892 or.2016.5077 After the publication of the article, the authors have realized (sic) that Figs. 3 and 7 in their paper were published with errors; in the first instance, regarding Fig. 3, panels u2018Cu2019 and u2018Du2019 contained partially overlapping data and were derived from the same original source, where these images were intended to show the effect of 2 ng ml sunitinib and 2 u00b5g ml HM-3, respectively, on cell migration. Likewise, in Fig. 7, panels u2018Cu2019 and u2018Du2019 also contained partially overlapping data derived from the same original source, even though these images were intended to show representative images for sections of tumor tissue from the HM-3 (3 mg kg) and HM-3 (48 mg kg) treatment groups. These errors arose inadvertently, as a consequence of the authors mishandling of their data. ,