Visfatin induces ovarian cancer resistance to anoikis by regulating mitochondrial activity - Abstract

Sep 24, 2026

Uploaded by Ezra

Ovarian cancer often relapses with peritoneal and distant metastasis, and circulating tumor spheroids must resist anoikis to survive without adhesion. Patient ascitic fluid contains elevated visfatin, known for anti-apoptotic effects, yet its mechanism in ovarian cancer spheroids is unclear. This study tests whether visfatin induces anoikis resistance and how mitochondrial activity and apoptotic pathways contribute to proliferation and survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Introduction

Materials and methods

Cell culture and chemicals

Results

Conclusion

Endocrine (2023) 80:448–458 [https://doi.org/10.1007/s12020-023-03305-x](https://doi.org/10.1007/s12020-023-03305-x) Visfatin induces ovarian cancer resistance to anoikis by regulating mitochondrial activity Justyna Gogola-Mruk 1 ● Wacław Tworzydło2 ● Kinga Krawczyk1 ● Weronika Marynowicz1 ● Anna Ptak1 Received: 19 October 2022 / Accepted: 9 January 2023 / Published online: 19 January 2023 © The Author(s) 2023 Abstract Purpose Ovarian cancer is characterized by recurrent peritoneal and distant metastasis. To survive in a non-adherent state,ﬂoating ovarian cancer spheroids develop mechanisms to resist anoikis. Moreover, ascitic ﬂuid from ovarian cancer patients contains high levels of visfatin with anti-apoptotic properties. However, the mechanism by which visfatin induces anoikis resistance in ovarian cancer spheroids remains unknown. Here, we aimed to assess wheather visfatin which possess antiapoptotic properties can induce resistance of anoikis in ovarian cancer spheroids. Methods Visfatin synthesis were examined using a commercial human visfatin ELISA Kit. Spheroid were exposed to visfatin and cell viability and caspase 3/7 activity were measured using CellTiter-Glo 3D cell viability assay and CaspaseGlo® 3/7 Assay System. mRNA and protein expression were analyzed by Real-time PCR and Western Blot analysis, respectively. Analysis of mitochondrial activity was estimated by JC-1 staining. Results First, our results suggested higher expression and secretion of visfatin by epithelial than by granulosa ovarian cells, and in non-cancer tissues versus cancer tissues. Interestingly, visfatin increased the proliferation/apoptosis ratio in ovarian cancer spheroids. Speciﬁcally, both the intrinsic and extrinsic pathways of anoikis were regulated by visfatin. Moreover, the effect of the visfatin inhibitor (FK866) was opposite to that of visfatin. Furthermore, both NAMPT and FK866 affected mitochondrial activity in ovarian cancer cells. Conclusion In conclusion, visfatin acts as an anti-apoptotic factor by regulating mitochondrial activity, leading to anoikis resistance in ovarian cancer spheroids. The ﬁnding suggest visfatin as a potential novel therapeutic target for the treatment of ovarian carcinoma with peritoneal dissemination. Keywords Visfatin ● Anoikis ● FK866 ● Mitochondrial activity ● Ovarian cancer Introduction Ovarian cancer, the gynecological malignancy with the highest mortality rate, is characterized by recurrent peritoneal and distant metastasis. Clinical and case studies report that ascitic ﬂuid contains ovarian cancer cells, either as single cells or as spheroid-like structures, which drive peritoneal dissemination [1, 2] . As a barrier against * Justyna Gogola-Mruk [justyna.gogola@uj.edu.pl](justyna.gogola@uj.edu.pl) 1 Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland 2 Department of Developmental Biology and Invertebrate Morphology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland metastases, normal cells undergo apoptosis after they lose contact with the extracellular matrix or neighboring cells. This cell death process is called “anoikis” [3] . Floating ovarian cancer spheroids have developed mechanisms to resist anoikis, and so have the ability to survive in a nonadherent state while traveling through the circulatory and lymphatic systems [4, 5] . Anoikis involves two apoptotic pathways: the cell death receptor (extrinsic) and mitochondrial (intrinsic) pathways. Likewise, blockade of the mitochondrial pathway, for example, via over-expression of anti-apoptotic Bcl-2 family proteins, can also induce resistance to anoikis [6] . Interestingly, ascites from ovarian cancer patients contains signiﬁcantly higher levels of visfatin (75.3± 28.1ng/mL) than serum; these high levels are associated intraperitoneal dissemination of ovarian cancer. The source of vis

FAQs

What is the main purpose of the study on visfatin and ovarian cancer spheroids?

To determine whether visfatin can induce resistance to anoikis in ovarian cancer spheroids, and to clarify the role of mitochondrial activity in that process.

How was anoikis resistance assessed in the experiments?

Spheroids were exposed to visfatin, and cell viability and caspase 3/7 activity were measured, along with analyses of mRNA/protein expression and mitochondrial activity via JC-1 staining.

What does the study conclude about visfatin’s mechanism?

Visfatin acts as an anti-apoptotic factor by regulating mitochondrial activity, which promotes anoikis resistance in ovarian cancer spheroids, and suggests visfatin as a potential therapeutic target.

Sep 24, 2026

Uploaded by Ezra