Advances in Clinical and Experimental Medicine
2020, vol. 29, nr 11, November, p. 1337–1345
Publication type: original article
License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)
Paclitaxel inhibits proliferation and invasion and promotes apoptosis of breast cancer cells by blocking activation of the PI3K/AKT signaling pathway
1 First Department of Oncology Surgery, Hangzhou Cancer Hospital, China
2 Fourth Department of Internal Medicine, Zibo City Traditional Chinese Medicine Hospital, China
3 Department of Pharmacy, The Second People’s Hospital of Liaocheng, China
4 Disinfection Supply Center, Maternal and Child Health Care of Zaozhuang, China
5 Department of Pharmacy, Hangzhou Cancer Hospital, China
Background. 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.
Objectives. To explore the effect and mechanism of PTX on the proliferation, apoptosis and invasiveness of breast cancer cells.
Material and Methods. 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).
Results. 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.
Conclusion. 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.
apoptosis, breast cancer, proliferation, paclitaxel, PI3K/AKt signaling pathway
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