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Tamoxifen induces ferroptosis in MCF-7 organoid
Lei Ye1, Fei Zhong1, Shishen Sun1
1Foshan Clinical Medical School, Guangzhou University of Chinese Medicine, Foshan, China.
Background:
Breast cancer is the most common female malignant tumor type globally. The occurrence and development of breast cancer involve ferroptosis, which is closely related to its treatment. The development of breast cancer organoids facilitates the analysis of breast cancer molecular background and tumor biological behavior, including clinical pathological characteristics, drug response, or drug resistance relationship, and promotes the advancement of precision treatment for breast cancer. The three-dimensional (3D) cell culture of breast cancer MCF-7 organoid is more similar to the in vivo environment and thus obtains more realistic results than 2D cell culture. Our study examined the new mechanism of tamoxifen in treating breast cancer through breast cancer MCF-7 organoids.
Methods:
We used 3D cells to culture breast cancer MCF-7 organoid, as well as tamoxifen-treated MCF-7 and tamoxifen-resistant MCF-7 (MCF-7 TAMR) cells. We used transcriptome sequencing. We detected GPX4 and SLC7A11 protein levels using Western blotting and the content of ATP, glutathione, and ferrous ions using the Cell Counting Lite 3D Kit. We assessed cell viability using the Cell Counting Kit-8 (CCK-8) assay.
Results:
Tamoxifen significantly inhibited the growth of MCF-7 organoids and significantly induced ferroptosis in MCF-7 organoids. The ferroptosis inhibitor reversed the significant tamoxifen-induced MCF-7 organoid inhibition activity. Moreover, the ferroptosis activator enhanced the tamoxifen-induced MCF-7 TAMR cell activity inhibition.
Conclusion:
Our study revealed that ferroptosis plays an important role in tamoxifen-induced MCF-7 organoid cell death and provides a new research idea for precise treatment of breast cancer through an organoid model.
Insights
Tamoxifen induces breast cancer cell death through ferroptosis. This study used organoids to reveal ferroptosis
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Breast cancer is a leading global malignancy in women.
- Ferroptosis, a form of regulated cell death, is implicated in breast cancer development and treatment.
- Three-dimensional (3D) organoid models offer a more in vivo-like environment for studying breast cancer compared to traditional 2D cultures.
Purpose of the Study:
- To investigate the mechanism of tamoxifen in treating breast cancer using MCF-7 organoids.
- To explore the role of ferroptosis in tamoxifen's efficacy against breast cancer.
Main Methods:
- Cultured breast cancer MCF-7 organoids, tamoxifen-treated MCF-7 cells, and tamoxifen-resistant MCF-7 (MCF-7 TAMR) cells in 3D.
- Utilized transcriptome sequencing, Western blotting for GPX4 and SLC7A11 protein levels, and assays for ATP, glutathione, and ferrous ion content.
- Assessed cell viability using the Cell Counting Kit-8 (CCK-8) assay.
Main Results:
- Tamoxifen significantly inhibited MCF-7 organoid growth and induced ferroptosis.
- A ferroptosis inhibitor reversed tamoxifen's inhibitory effect on MCF-7 organoids.
- A ferroptosis activator enhanced tamoxifen's inhibitory effect on MCF-7 TAMR cells.
Conclusions:
- Ferroptosis is a key mechanism in tamoxifen-induced cell death in breast cancer organoids.
- These findings provide a novel organoid-based approach for precise breast cancer treatment strategies.
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