Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma

by Selleckchem | Jan 07 2024

Overcoming resistance to radiation is a major challenge in cancer treatment. Stearoyl-coa desaturase (SCD1) is the enzyme responsible for oleic acid (OA) and palmitoleic acid (POA) formation. Here, we provided evidence that targeting SCD1 was capable of inducing ferroptosis and immunogenic cell death (ICD), thereby improving the radiation sensitivity of esophageal squamous cell carcinoma (ESCC). ESCC cell lines with high SCD1 expression were treated with MF-438 (SCD1 inhibitor) to determine cell viability. Colony formation assay was performed to evaluate the radiation sensitization of SCD1 inhibitor. Tumor cell ferroptosis and ICD was analyzed in MF-438, radiation therapy (RT) and the combination treatment group. The potential molecular mechanisms underlying MF-438 as a novel radiation sensitizer in ESCC were explored. We concluded by assessing SCD1 as a prognostic factor in ESCC. MF-438 exhibited antitumor activity in ESCC cells. Our outcomes revealed significant improvement of radiation sensitivity by MF-438. Moreover, the combination treatment enhanced tumor cell ferroptosis and ICD. Further analyses revealed SCD1 conferred radiation resistance via alleviating ferroptosis in tumor cells; targeting SCD1 inhibited the biosynthesis of OA and POA, and improved radiation induced ferroptosis in ESCC cells. Clinical analysis indicated high expression of SCD1 was associated with unfavorable survival in patients of ESCC. In summary, our results demonstrated that MF-438 acted as a ferroptosis inducer. Targeting SCD1 conferred the immunogenicity of ferroptotic cancer cells and increased the effectiveness of RT in ESCC. SCD1 could be considered as a useful prognostic indicator of survival in ESCC.

Comments:

It seems like you've summarized a study that explores the potential of targeting Stearoyl-coa desaturase 1 (SCD1) in enhancing the effectiveness of radiation therapy for esophageal squamous cell carcinoma (ESCC). Targeting SCD1 with MF-438, an SCD1 inhibitor, showed promising results in inducing ferroptosis and immunogenic cell death (ICD), thus improving the sensitivity of ESCC to radiation therapy.

The study employed various assays including cell viability tests, colony formation assays, and analysis of ferroptosis and ICD in different treatment groups. The findings suggested that targeting SCD1 using MF-438 enhanced radiation sensitivity, increased tumor cell ferroptosis, and improved immunogenic cell death when combined with radiation therapy in ESCC cell lines.

Furthermore, the study explored the molecular mechanisms behind MF-438's role as a radiation sensitizer, indicating that SCD1 might confer radiation resistance by mitigating ferroptosis in tumor cells. Inhibiting SCD1 led to a reduction in oleic acid (OA) and palmitoleic acid (POA) synthesis, consequently improving radiation-induced ferroptosis in ESCC cells.

Additionally, the clinical analysis suggested that high expression of SCD1 was associated with poorer survival outcomes in ESCC patients, implying SCD1 could potentially serve as a prognostic indicator for ESCC.

In summary, the study demonstrates that targeting SCD1 with MF-438 induces ferroptosis, enhances immunogenicity in ferroptotic cancer cells, and increases the effectiveness of radiation therapy in ESCC. Moreover, SCD1 expression levels might have prognostic significance in determining survival outcomes for ESCC patients.