Abstract
Breast cancer has the highest incidence and mortality among all cancers in women. Paclitaxel (PTX) has a notable therapeutic effect on cancer in clinical practice. To explore the effect and mechanism of PTX on the proliferation, apoptosis and invasiveness of breast cancer cells. MCF-7 cells were treated with PTX (0 μM, 0.01 μM, 0.1 μM, 1 μM) for 48 h. Cell viability was detected using MTT assay and lactate dehydrogenase (LDH) assay; the cell proliferation rate was detected using 5-ethynyl-2'-deoxyuridine (EdU) assay to screen the most effective concentration of PTX. MCF-7 cells were then divided into 5 groups: control group, PTX group, oe-PI3K group, NC-PI3K group, and oe-PI3K+PTX group. Cell apoptosis and cell cycles were detected with flow cytometry; cell invasion was determined using a transwell assay; western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to measure the mRNA and protein expression level of cleaved caspase-3, Bax, Bcl-2, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), p-AKT (Thr308), and p-AKT (Ser473). Paclitaxel inhibited cell viability and proliferation in a dose-dependent manner. In the PTX group, the apoptosis rate, the number of cells arrested in the G2/M phase and the expression levels of Cleaved caspase-3 and Bax were increased, but the number of invasive cells and the expression levels of Bcl-2, MMP-9, vascular endothelial growth factor (VEGF), p-AKT (Thr308), and p-AKT (Ser473) were decreased. However, PI3K upregulation can reverse the effects of PTX. Paclitaxel could inhibit MCF-7 cell proliferation and invasion, and promote MCF-7 cell apoptosis by downregulating the expression of p-AKT (Thr308) and p-AKT (Ser473) in the PI3K/AKT signaling pathway.
Highlights
Breast cancer is the most common gynecological cancer, with the highest mortality rate
In the PTX group, the apoptosis rate, the number of cells arrested in the G2/M phase and the expression levels of Cleaved caspase-3 and Bax were increased, but the number of invasive cells and the expression levels of Bcl-2, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), p-AKT (Thr308), and p-AKT (Ser473) were decreased
The expression of PI3K/AKT signaling pathway-related protein p-AKT/AKT in the MCF-7, BT-549, MDA-MB-231, T47D, and MCF-10A cell lines was detected with western blot (Fig. 1A)
Summary
Breast cancer is the most common gynecological cancer, with the highest mortality rate. There are many factors affecting the prevalence of breast cancer, including family history, age, smoking and drinking, early amenorrhea, delayed menarche, obesity, and high-fat diet; oral contraceptives or other exogenous estrogens can increase the incidence of breast cancer.[4–6]. It is a highly heterogeneous disease – its clinical characteristics and biological behavior vary widely among patients; survival varies from person to person.[7]. Fully understanding the mechanism of action of chemotherapy drugs may help improve the therapeutic outcome of breast cancer. Breast cancer has the highest incidence and mortality among all cancers in women. Paclitaxel (PTX) has a notable therapeutic effect on cancer in clinical practice
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