EGFR inhibitor C225 Increases the Radio-Sensitivity of Human Breast Cancer Cells

Abstract

Objective: This study was undertaken to investigate the effect of C225 on the radio-sensitivity of MDA-MB-231 cells line and to disclosure underlying mechanism. Methods: CCK8 assay was used to measure the proliferation inhibition of C225 on MDA-MB-231 cells. The combined effects of C225 plus radiation on the proliferation of MDA-MB-231 cells were also evaluated by CCK-8 assay. The clonogenic assay was performed to evaluate the cell surviving fractions and to determine the radio-sensitizing effect of C225 on MDA-MB-231 cells. The apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blot analysis was used to detect the expression of p-EGFR, p-Akt, p-P38, and caspase-3. Results: C225 had an inhibiting effect on the proliferation of cells in a concentration-dependent manner. The cloning formation capacity was decreased in C225 plus radiation group. C225 increased radio-sensitivity of cells and led to cell cycle arrest in G0/G1 phase markedly. Cells treated with C225 and radiation predominantly exhibited G0/G1 phase arrest and significant decreased in the fraction of cells in the S phase. Moreover, C225 and radiation significantly increased the apoptosis rate of cells. Decreased cell proliferation was further supported by the down-regulation of p-EGFR and its downstream singling pathway proteins such as p-Akt and p-P38. The up-regulation of the Caspase-3 expression in C225 plus radiation group revealed that C225 could increase radiation-inducing cell apoptosis. Conclusion: C225 could increase the radio-sensitivity of cells, which may be due to the anti-proliferative synergistic effect between C225 and radiation as well as the down-regulation of the PI3K/Akt signaling pathway.

Combined treatment with silver graphene quantum dot, radiation, and 17‐AAG induces anticancer effects in breast cancer cells

“…Likewise, C225 block the activation of EGFR that could improve the radio-sensitivity of BC cells. It has been reported that this effect may be associated with the antiproliferative synergistic effect between radiation and C225 (Yao et al, 2019). Also, anti-EGFR monoclonal antibody-conjugated hollow gold nanospheres can increases radiocytotoxic targeting in megavoltage radiation energies of cervical cancer (Liu, Liang, Liu, Li, & Yang, 2015).…”

Modulating the Radiation Response for Improved Outcomes in Breast Cancer

“…However, as EGFR inhibition has become a more relevant treatment strategy in other cancers, newer and more specific EGFR inhibitors such as cetuximab, canertinib, panitumumab, and nimotuzumab have become available, with similar preclinical radiosensitizing effects in breast cancer. [89][90][91][92] Consistent with existing data for HER2 and EGFR signaling, EGFR3-mediated signaling is radioprotective in breast cancer cells, 93,94 but because of the overlap between EGFR signaling pathway signaling, further comparative studies are needed to make direct conclusions comparing the efficacy of specific inhibition of each of the EGFR family members. Furthermore, overexpression of the dominant-negative, truncated EGFR-CD533 protein leads to radiosensitization of breast cancer cells after repeated doses of radiation therapy (RT), 95,96 whereas overexpression of TOB1, a negative regulator of HER2 activity, is radiosensitizing.…”

The Effect of PEI-Mediated E1A on the Radiosensitivity of Hepatic Carcinoma Cells

“…Cell cycle regulation is an important factor to determine the radiation sensitivity of tumor cells (Yao et al, 2019). It is well known that different cell cycle phases have different radiosensitivity.…”