Orlistat, an anti-obesity drug, suppressed osteosarcoma progression and potentiated pd1ab immune checkpoint blockade therapy via upregulation of serpinf1

Wang, Chan; Fang, Binbo; Fu, Hanzhang; Li, Shumin

doi:10.1590/s2175-97902025e24279

home Tabla de contenido navigate_before Anterior Actual Siguiente navigate_next

Texto (Inglés)

Download PDF (Inglês)

Texto (Inglés)
Download PDF (Inglês) (abre em nova aba)

Whatsapp
BlueSky
Mastodon
Facebook
Mais

home Tabla de contenido

Whatsapp
BlueSky
Mastodon
Facebook
Mais

Texto (Inglés)

Download PDF (Inglês) (abre em nova aba)

Article • Braz. J. Pharm. Sci. 61 • 2025 • https://doi.org/10.1590/s2175-97902025e24279 linkcopy

Orlistat, an anti-obesity drug, suppressed osteosarcoma progression and potentiated pd1ab immune checkpoint blockade therapy via upregulation of serpinf1

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Orlistat(Orli) is a safe and effective drug for obesity treatment approved by the Food and Drug Administration (FDA) in the US. Recently, Orli has been reported to exert considerable antitumor effects in amount types of malignancy. However, its role in osteosarcoma (OS) progression and its clinical significance in tumor therapy such as immune therapy remains largely unknown. In this study, we detected the effect of Orli exerted on OS progression using CCK-8 assay, wound-healing assay, Enzyme-linked immunosorbent assay (ELISA), cell transfection and xenograft growth assay. The result indicated that by upregulating Serpin Family F member 1 (SERPINF1), a multifunctional protein, OS inhibited OS progression via suppressing proliferation, colony-forming, migration and angiogenesis ability of OS cells in vitro and in vivo. More importantly, Orli potentiated programmed death1 antibody (PD1ab) immune checkpoint blockade therapy and may candidate as a potential drug in OS therapy.

Keywords:
Orlistat; Osteosarcoma; SERPINF1; Programmed death1 antibody

Authorship

person Chan Wang

carried out the experiments · read and approved the final manuscript

schoolDepartment of orthopedics, Yuhuan Second People's Hospital, Yuhuan, Zhejiang, ChinaDepartment of orthopedicsChinaYuhuan, Zhejiang, ChinaDepartment of orthopedics, Yuhuan Second People's Hospital, Yuhuan, Zhejiang, China

person Binbo Fang

performed statistical analysis · carried out the experiments · read and approved the final manuscript

schoolDepartment of Medicine, Taizhou University, Zhejiang, ChinaDepartment of MedicineChinaZhejiang, ChinaDepartment of Medicine, Taizhou University, Zhejiang, China

person Hanzhang Fu

carried out the experiments · performed statistical analysis · read and approved the final manuscript

schoolDepartment of Medicine, Taizhou University, Zhejiang, ChinaDepartment of MedicineChinaZhejiang, ChinaDepartment of Medicine, Taizhou University, Zhejiang, China

person Shumin Li *

read and approved the final manuscript · performed data analysis and interpretation · study design and prepared the manuscript

0009-0005-0118-8601

person*Correspondence: S. Li, Department of Orthopedics, Yuhuan Second People's Hospital, No.77, Environmental Protection Middle Road, Chumen Town, Yuhuan City, Taizhou City, Zhejiang, China, E-mail:
15395761515@163.com

Associated Editor:

Moacyr Rêgo

SCIMAGO INSTITUTIONS RANKINGS

Department of orthopedics, Yuhuan Second People's Hospital, Yuhuan, Zhejiang, ChinaDepartment of orthopedicsChinaYuhuan, Zhejiang, ChinaDepartment of orthopedics, Yuhuan Second People's Hospital, Yuhuan, Zhejiang, China

Department of Medicine, Taizhou University, Zhejiang, ChinaDepartment of MedicineChinaZhejiang, ChinaDepartment of Medicine, Taizhou University, Zhejiang, China

Figures

Figures (6)

Thumbnail

FIGURE 1 Orli inhibited the proliferation, colony-forming, migration and angiogenesis ability of OS cells in vitro. (A-C) Cell viability of K7M2(A), Saos-2 cells (B) and MG63(C) were measured by the CCK-8 assay after with various concentrations of Orli treatment (0 µM, 10 µM, 100 µM) and as DOX (doxorubicin, 0.1µM) as positive control, n=3; (D) Cell colony-formation ability of MG63 cells after treatment with Orli (100 µM) or DOX (doxorubicin, 0.1µM) as positive control, n=3; (E-F) ELISA detection on VEGF secretion of MG63 and K7M2 cells after treatment with Orli (100 µM) or DOX (doxorubicin, 0.1µM); (G-H) Cell migration capacity of MG63 cells after treatment with Orli (100 µM) or DOX (doxorubicin, 0.05µM) as positive control was tested through wound healing assays (G) and their quantitative analysis(H), n=3.

Thumbnail

FIGURE 2 Orli suppressed tumorigenicity of both murine and human OS cells in vivo. (A) Schematic representation of Orli treatment on K7M2 tumors on BALB/c mice or MG63 tumors on nude mice; (B) Representative photo of K7M2 subcutaneous tumor models; (C) curve of K7M2 tumor size in each group; (D) weight of K7M2 tumor in each group; (E) Representative photo of MG63 xenograft models; (F) curve of MG63 tumor size in each group; (G) weight of MG63 tumor in each group.

Thumbnail

FIGURE 3 Orli suppressed OS progression via modulating SERPINF1. (A) SERPINF1 expression in OS cell lines (Saos-2, HOS , U2OS, and MG63) and a human normal osteoblast cell line (hFOB1.19) detected by Qpcr; (B) SERPINF1 expression in MG63 (B) after Orli treatment (10µM, 50µM, 100µM) detected by Qpcr; (C) The efficiency of SERPINF1 knock down detected by Qpcr; (D-E) Cell viability of MG63 (D) and K7M2(E) after knocking down SERPINF1 expression and Orli (100 µM); treatment; (F-G)VEGF secretion of MG63 (F) and K7M2(G) after knocking down SERPINF1 expression and Orli (100 µM).

Thumbnail

FIGURE 4 Orli enhanced PD1ab therapy by upregulating SERPINF1 expression. (A) Scheme representing the experimental procedure including Orli (100mg/kg, i.p.) and PD1ab (200µg per mouse, i.p.) treatment on BALB/C mice; (B) Representative images of wild-type K7M2 tumors and SH-SERPINF1 tumors after treatment; (C-D) Curve growth curves of wild-type K7M2 tumors(C) and SH-SERPINF1 tumors (D); (D) tumor burdens of wild-type K7M2 tumors and SH-SERPINF1 tumors after treatment.

Thumbnail

FIGURE 5 A schematic diagram illustrating Orli impaired the proliferation, migration and angiogenesis capacity of OS cell and potentiate PD1ab therapy via upregulating SERPINF1.

Thumbnail

FIGURE S1 (A) Representative images of K7M2 tumors after treatment with Oril (0, 50mg/kg, 100mg/kg); (B) Weight of tumors; (C–D) IHC analysis of CD31+ vessels of MG63 tumor tissue after Oril (100mg/kg) treatment; (C) Representative IHC images; (D) MVD of tumor tissue; (E–F)IHC analysis of CD8+ T cell infiltration of K7-M2 tumor tissue after Oril treatment; (E) Representative IHC images, negative control, sections without using primary CD8 antibody; positive control: mice spleen section staining with primary CD8 antibody; (F) Number of CD8⁺ T cell infiltration of K7-M2 tumor tissue after Oril treatment. Scale bar, 20μm. **p < 0.01.

imageFIGURE 1 Orli inhibited the proliferation, colony-forming, migration and angiogenesis ability of OS cells in vitro. (A-C) Cell viability of K7M2(A), Saos-2 cells (B) and MG63(C) were measured by the CCK-8 assay after with various concentrations of Orli treatment (0 µM, 10 µM, 100 µM) and as DOX (doxorubicin, 0.1µM) as positive control, n=3; (D) Cell colony-formation ability of MG63 cells after treatment with Orli (100 µM) or DOX (doxorubicin, 0.1µM) as positive control, n=3; (E-F) ELISA detection on VEGF secretion of MG63 and K7M2 cells after treatment with Orli (100 µM) or DOX (doxorubicin, 0.1µM); (G-H) Cell migration capacity of MG63 cells after treatment with Orli (100 µM) or DOX (doxorubicin, 0.05µM) as positive control was tested through wound healing assays (G) and their quantitative analysis(H), n=3. open_in_new

imageFIGURE 2 Orli suppressed tumorigenicity of both murine and human OS cells in vivo. (A) Schematic representation of Orli treatment on K7M2 tumors on BALB/c mice or MG63 tumors on nude mice; (B) Representative photo of K7M2 subcutaneous tumor models; (C) curve of K7M2 tumor size in each group; (D) weight of K7M2 tumor in each group; (E) Representative photo of MG63 xenograft models; (F) curve of MG63 tumor size in each group; (G) weight of MG63 tumor in each group. open_in_new

imageFIGURE 3 Orli suppressed OS progression via modulating SERPINF1. (A) SERPINF1 expression in OS cell lines (Saos-2, HOS , U2OS, and MG63) and a human normal osteoblast cell line (hFOB1.19) detected by Qpcr; (B) SERPINF1 expression in MG63 (B) after Orli treatment (10µM, 50µM, 100µM) detected by Qpcr; (C) The efficiency of SERPINF1 knock down detected by Qpcr; (D-E) Cell viability of MG63 (D) and K7M2(E) after knocking down SERPINF1 expression and Orli (100 µM); treatment; (F-G)VEGF secretion of MG63 (F) and K7M2(G) after knocking down SERPINF1 expression and Orli (100 µM). open_in_new

imageFIGURE 4 Orli enhanced PD1ab therapy by upregulating SERPINF1 expression. (A) Scheme representing the experimental procedure including Orli (100mg/kg, i.p.) and PD1ab (200µg per mouse, i.p.) treatment on BALB/C mice; (B) Representative images of wild-type K7M2 tumors and SH-SERPINF1 tumors after treatment; (C-D) Curve growth curves of wild-type K7M2 tumors(C) and SH-SERPINF1 tumors (D); (D) tumor burdens of wild-type K7M2 tumors and SH-SERPINF1 tumors after treatment. open_in_new

imageFIGURE 5 A schematic diagram illustrating Orli impaired the proliferation, migration and angiogenesis capacity of OS cell and potentiate PD1ab therapy via upregulating SERPINF1. open_in_new

imageFIGURE S1 (A) Representative images of K7M2 tumors after treatment with Oril (0, 50mg/kg, 100mg/kg); (B) Weight of tumors; (C–D) IHC analysis of CD31+ vessels of MG63 tumor tissue after Oril (100mg/kg) treatment; (C) Representative IHC images; (D) MVD of tumor tissue; (E–F)IHC analysis of CD8+ T cell infiltration of K7-M2 tumor tissue after Oril treatment; (E) Representative IHC images, negative control, sections without using primary CD8 antibody; positive control: mice spleen section staining with primary CD8 antibody; (F) Number of CD8⁺ T cell infiltration of K7-M2 tumor tissue after Oril treatment. Scale bar, 20μm. **p < 0.01. open_in_new

How to cite

linkcopy

Ferramentas do artigo

PDFs
Métricas
Figuras e tabelas
Versiones y traducciones
Como citar este artículo
Artículos relacionados

location_on

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

rss_feed Acompañe los números de esta revista en su lector de RSS

Versão para download de PDF

PDF

Inglés

Versões e tradução automática

Escolha a versão original do texto ou utilize um serviço de tradução automática.

Versão original do texto

English

Tradução automática

Google Translator (abre serviço externo de tradução)
Microsoft Translator (abre serviço externo de tradução)

Como citar

Escolha um formato para exportar ou selecione um estilo de citação. O conteúdo abaixo pode ser atualizado após a seleção.

Baixar em RIS

Baixar em BIBTEX

Outros formatos de citação e exportação: