Related Experiment Video
Updated: Dec 29, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Interleukin-22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway
Zhiqiang Li1, Renjie Xu1, Xiangxin Zhang1
1Department of Orthopedics, Nanjing Medical University Affiliated Suzhou Hospital (Suzhou Municipal Hospital), Suzhou, Jiangsu 215002, P.R. China.
Abstract:
The present study aimed to investigate the regulatory mechanisms by which interleukin (IL)-22 regulates cisplatin (DDP) sensitivity in osteosarcoma cells. Firstly, reverse transcription-quantitative (RT-q) PCR and western blotting demonstrated that IL-22 expression was significantly increased in osteosarcoma tissues and cell lines compared with the adjacent normal tissues and the normal osteoblast hFOB1.19 cells. Subsequently, the MG63 osteosarcoma cell line and cisplatin-resistant MG63/DDP osteosarcoma cell line were treated with different concentrations of cisplatin (2.5, 5.0, 10, 20, 40 and 80 µg/ml), and the half maximal inhibitory concentration (IC50) was calculated based on the MTT assay. The results showed that the IC50 of DDP in MG63/DDP cells was significantly higher than that in MG63 cells. Furthermore, IL-22 expression was higher in MG63/DDP cells compared with MG63 cells. Subsequently, the effects of IL-22 downregulation and overexpression on MG63/DDP and MG63 cells were assessed using the MTT assay, flow cytometry, RT-qPCR and western blotting. The IL-22 small interfering (si) RNA in MG63/DDP cells significantly decreased the IC50 of DDP and decreased the cell viability of MG63/DDP cells. Furthermore, IL-22 RNA interference decreased BCl-2 expression and phosphorylation of STAT3, induced apoptosis, and increased the expression of Bax and cleaved caspase-3. The IL-22 overexpression plasmid had opposite effects to the observations in IL-22 siRNA-transfected MG63 cells. Overall, the present study indicated that IL-22 regulated the cell viability and apoptosis of osteosarcoma cells by regulating the activation of the STAT3 signaling pathway and affecting the expression of apoptosis-associated genes, and thereby mediating the sensitivity of osteosarcoma cells to cisplatin.
Insights
Interleukin-22 (IL-22) increases resistance to cisplatin (DDP) in osteosarcoma by activating STAT3 signaling. Reducing IL-22 enhances DDP sensitivity and promotes apoptosis in osteosarcoma cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Cisplatin (DDP) is a common chemotherapy agent, but resistance is a significant clinical challenge.
- Interleukin-22 (IL-22) is implicated in various cellular processes, including cancer progression.
Purpose of the Study:
- To investigate the role of IL-22 in regulating cisplatin sensitivity in osteosarcoma.
- To elucidate the molecular mechanisms underlying IL-22's effect on DDP resistance.
- To explore potential therapeutic strategies targeting IL-22 in osteosarcoma treatment.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blotting to assess IL-22 expression.
- MTT assay to determine half maximal inhibitory concentration (IC50) of DDP.
- RNA interference (siRNA) and overexpression plasmids to manipulate IL-22 levels.
- Flow cytometry to analyze apoptosis.
- Analysis of apoptosis-related genes (Bcl-2, Bax, cleaved caspase-3) and STAT3 signaling pathway activation.
Main Results:
- IL-22 expression was significantly upregulated in osteosarcoma tissues and cell lines, particularly in cisplatin-resistant cells (MG63/DDP).
- IL-22 downregulation using siRNA in MG63/DDP cells decreased DDP IC50 and cell viability, while increasing apoptosis.
- IL-22 knockdown reduced Bcl-2 expression, decreased STAT3 phosphorylation, and increased Bax and cleaved caspase-3 expression.
- IL-22 overexpression in sensitive cells (MG63) had opposite effects, suggesting a pro-resistance role.
Conclusions:
- IL-22 promotes cisplatin resistance in osteosarcoma by enhancing cell viability and inhibiting apoptosis.
- The mechanism involves the regulation of STAT3 signaling pathway activation and apoptosis-associated gene expression.
- Targeting IL-22 may represent a novel therapeutic approach to overcome cisplatin resistance in osteosarcoma.
More Related Videos
11:15A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
04:25Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
