The simultaneous use of CRISPR/Cas9 to knock out the PI3Kca gene with radiation to enhance radiosensitivity and inhibit tumor growth in breast cancer

Objective(s): Breast neoplasm is a malignancy that can have a poor prognosis. The PI3K/AKT signaling pathway is frequently activated in various tumor types, including breast cancer, leading to alterations in the tumor microenvironment and radioresistance. Selective inhibition of PI3Kca (p110α) has been considered an alternative approach to overcome radioresistance, owing to concerns surrounding the excessive side effects of pan-PI3K inhibitors tested in clinical trials. This investigation aimed to evaluate the efficacy of co-administering PI3Kca knocking out with radiation therapy in mitigating radioresistance and suppressing tumor growth in the MDA-MB-231 cell line. Materials and Methods: The present investigation utilized the CRISPR/Cas9 technique to induce a knockout of the PI3Kca gene. Subsequently, after 24 hr of transfection, gene expression, cell proliferation, apoptosis rate, and angiogenesis were assessed. Results: We demonstrated that knocking out PI3Kca, in combination with radiation, increased apoptosis, reduced the expression of PI3Kca and AKT1 genes, and decreased cell proliferation. The CAM assay analysis has demonstrated that knocking out the PI3Kca gene and radiotherapy substantially reduced the total vessel network length and the number of junctions.Conclusion: The findings of our investigation indicate that the integration of radiation therapy with PI3Kca yielded enhanced radiosensitivity, leading to a marked retardation of tumor progression and an increased survival rate.