Abstract:
In clinical practice, it is also common to see tumor recurrence with distant metastasis in breast cancer patients after chemotherapy, which leads to increased mortality of breast cancer patients. Therefore, it is of great theoretical significance and practical clinical application to further investigate the molecular mechanism of enhanced invasive metastatic ability caused by chemotherapy drugs, and to further search for feasible target molecules that can effectively interfere with them to prevent the occurrence of enhanced invasive metastatic properties of tumors during chemotherapy. Real-time fluorescence PCR showed that the expression levels of tumor tissue mesenchymal cell-related markers: VIM, CDH1 and TWIST1 genes were significantly increased in patients who received neoadjuvant chemotherapy compared with breast cancer patients who did not receive neoadjuvant chemotherapy, while the expression of epithelial cell-related marker CDH1 was decreased, and the results indicated that neoadjuvant chemotherapy could inhibit EMT in breast cancer cells. Flow cytometry detected the expression of stem cell marker CD44/CD24 in primary breast cancer cells before and after chemotherapy, and found that the proportion of tumor stem cells was significantly increased in primary tumor cells treated with neoadjuvant chemotherapy. To further clarify the role of chemotherapy on EMT transformation of breast cancer cells, we used qPCR to detect the expression levels of CDH1 and VIM in MCF-7 and MDA-MB-231 cells after treatment with adriamycin, and the results showed that adriamycin treatment significantly promoted EMT in MCF-7 and MDA-MB-231 cells. Moreover, we used transwell assay to detect the alteration of cell migration ability, and we observed that adriamycin treatment significantly promoted the migration ability of MCF-7 and MDA-MB-231 cells after adriamycin treatment. We found a significant increase in the expression level of FOXM1 in breast cancer cells that underwent mesenchymal transformation in response to chemotherapeutic agents. qRT-PCR and WB results showed that the expression of FOXM1 mRNA and protein in MCF and MDA-MB-231 cells was significantly increased. Subsequently, we found by flow cytometry that overexpression of FOXM1 in MCF and MDA-MB-231 cells promoted an increased CD44+/CD24- cell ratio and an increased number of microsomes. CCK8 experiments further showed that the proliferation capacity of MCF and MDA-MB-231 cells overexpressing FOXM1 was significantly increased compared with control normal cells. FOXM1 can affect EMT in breast cancer cells, thereby promoting tumor stem cell proliferation. Inhibition of FOXM1 expression may affect clinical chemotherapeutic efficacy in breast cancer patients.
Audience Take Away Notes:
- Neoadjuvant chemotherapy could inhibit EMT in breast cancer cells
- We found a significant increase in the expression level of FOXM1 in breast cancer cells that underwent mesenchymal transformation in response to chemotherapeutic agents
- FOXM1 can affect EMT in breast cancer cells, thereby promoting tumor stem cell proliferation. Inhibition of FOXM1 expression may affect clinical chemotherapeutic efficacy in breast cancer patients
