Astaxanthin-loaded PLGA nanoparticles - inhibit survival of MKN-45 gastric cancer cell line by modulating JAK2/STAT3/mTOR/PI3K pathway

Q: What problem does the study address regarding gastric cancer therapy?

It targets the need for new therapeutic strategies because gastric cancer has poor prognosis and existing treatments can cause unwanted side effects and drug resistance.

Q: How were ASX-loaded PLGA nanoparticles evaluated in the MKN-45 gastric cancer model?

Cell viability and survival were measured using an MTT assay, clonogenic assays assessed reproductive power and colony formation, and apoptosis/necrosis-related cell death was assessed with AO staining.

Q: What did the results show about the JAK2/STAT3/mTOR/PI3K pathway after ASX + PLGA treatment?

ASX + PLGA increased expression and intensity of JAK2, STAT3, and mTOR, while decreasing phosphorylated forms of JAK2, STAT3, and mTOR compared with the control group.

Sep 23, 2026

Uploaded by Himbo

Gastric cancer remains a major global health challenge with high incidence and poor outcomes, while side effects and drug resistance limit current therapies. This research evaluates how astaxanthin (ASX) delivered via PLGA nanoparticles affects the survival of MKN-45 gastric cancer cells and the signaling balance within the JAK2/STAT3/mTOR/PI3K pathway. ASX-loaded formulations reduced viability in a dose-dependent manner, modulating both total and phosphorylated pathway proteins.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Background/aims

Methods

Results

Conclusions

Keywords

Background

YektaKooshali etal. BMC Cancer (2025) 25:44 [https://doi.org/10.1186/s12885-024-13401-4](https://doi.org/10.1186/s12885-024-13401-4) BMC Cancer RESEARCH Open Access Astaxanthin-loaded PLGA nanoparticles inhibit survival of MKN-45 gastric cancer cell line by modulating JAK2/STAT3/mTOR/PI3K pathway Mohammad Hossein YektaKooshali1,2, Mahdieh SobhZahedi3*, Seyed Mohammad Taghi Razavi Tousi1, Masoud Hamidi4 and Leila Modiri2* Abstract Background/aims Gastric cancer (GC) is a significant global health issue with high incidence rates and poor prognoses, ranking among the top prevalent cancers worldwide. Due to undesirable side effects and drug resistance, there is a pressing need for the development of novel therapeutic strategies. Understanding the interconnectedness of the JAK2/STAT3/mTOR/PI3K pathway in tumorigenesis and the role ofAstaxanthin (ASX), a red ketocarotenoid member of xanthophylls and potent antioxidant and anti-tumor activity, can be effective for cancer treatments. This study aimed to investigate the effect of ASX-loaded nanoparticles on the survival of MKN-45 GC cells and the expression of JAK2/STAT3/mTOR/PI3K, offering insights into potential targeted therapies for GC. Methods The growth status and survival rate of MKN-45 GC cell lines were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT) assay, and the optimal IC50 concentration of ASX, PLGA, and ASX + PLGA was estimated. Also, the clonogenic assay was performed to determine the reproductive power and colony formation of under-treatment cells. Apoptosis and necroptosis of cells were evaluated using acridine orange (AO) staining. The western blot assessed the protein’s level of expression and intensity (JAK2/STAT3/mTOR/PI3K) . SPSS version 16 software was used for statistical analysis, P-value was considered lower than 0.05. Results Based on the results, increasing concentrations of ASX and ASX + PLGA led to a decrease in the viability of MKN-45 cells compared to the control group (P < 0. 001) . This value was lower for cells treated with ASX + PLGA (P = 0 . 003) . The IC50 values for each of the studied groups (ASX, ASX + PLGA, and PLGA) were 81.45 µg/ml, 51.45 µg/ml, and 3.383 mg/ml, respectively. The levels of expression and intensity ofJAK2, STAT3, and mTOR proteins in the Western blotting analysis under ASX + PLGA treatment increased compared to the control group. Conversely, the levels of expression and intensity of P-JAK2, P-STAT3, and P-mTOR proteins in the ASX + PLGA treatment group decreased by 41%, 34%, 37%, and 43%, respectively, compared to the control group. Protein expression levels and intensities of JAK2, STAT3, and mTOR significantly increased when treated with PLGA, ASX, and ASX + PLGA compared to the control group (P < 0. 001) . Conclusions The encapsulation of ASX in PLGA nanoparticles enhances drug stability, enables targeted deliv ery, and allows for sustained release. This study highlights the therapeutic potential of ASX-loaded nanoparticles *Correspondence: Mahdieh SobhZahedi [mahdieh.sobhzahedi@yahoo.com](mahdieh.sobhzahedi@yahoo.com)[ ](mahdieh.sobhzahedi@yahoo.com)Leila Modiri [Leim_clinpathem@yahoo.com](Leim_clinpathem@yahoo.com) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated o

FAQs

What problem does the study address regarding gastric cancer therapy?

It targets the need for new therapeutic strategies because gastric cancer has poor prognosis and existing treatments can cause unwanted side effects and drug resistance.

How were ASX-loaded PLGA nanoparticles evaluated in the MKN-45 gastric cancer model?

Cell viability and survival were measured using an MTT assay, clonogenic assays assessed reproductive power and colony formation, and apoptosis/necrosis-related cell death was assessed with AO staining.

What did the results show about the JAK2/STAT3/mTOR/PI3K pathway after ASX + PLGA treatment?

ASX + PLGA increased expression and intensity of JAK2, STAT3, and mTOR, while decreasing phosphorylated forms of JAK2, STAT3, and mTOR compared with the control group.

Sep 23, 2026

Uploaded by Himbo