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 of Astaxanthin (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.
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 of Astaxanthin (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.
Conclusions
The encapsulation of ASX in PLGA nanoparticles enhances drug stability, enables targeted delivery, and allows for sustained release. This study highlights the therapeutic potential of ASX-loaded nanoparticles in targeting JAK2/STAT3/mTOR/PI3K pathways in GC treatment. Further research is needed to understand the mechanisms and clinical applications of this novel immunotherapy strategy.
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 of JAK2, 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 delivery, and allows for sustained release. This study highlights the therapeutic potential of ASX-loaded nanoparticles in targeting JAK2/STAT3/mTOR/PI3K pathways in GC treatment. Further research is needed to understand the mechanisms and clinical applications of this novel immunotherapy strategy.