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Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway

  • Authors:
    • Yuwan Zhao
    • Xin Zeng
    • Huancheng Tang
    • Dongcai Ye
    • Jianjun Liu

  • View Affiliations

  • Published online on: March 6, 2019     https://doi.org/10.3892/ol.2019.10119
  • Pages: 4277-4284

  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have reported that metformin (MET) has anticancer activity. In combination with chemotherapeutic drugs, MET reduces the dosage of chemotherapeutic drugs required and enhances anticancer efficacy. In the present study, the combination of MET and paclitaxel (PTX) in three human prostate cancer (PCa) cell lines (22RV1, PC‑3 and LNCaP) was evaluated to investigate the effects on proliferation and apoptosis of PCa cells. The present study explored whether their effects were associated with reactive oxygen species (ROS). An MTT assay and microscopy were used to study the effect of MET + PTX on cell growth. Half maximal inhibitory concentration (IC50) values were obtained for MET (12.281±1.089 mM for 22RV1, 2.248±0.352 mM for PC‑3 cells and 3.610±0.577 mM for LNCaP cells) and PTX (13.170±1.12 nM for PC‑3 cells) at 48 h. Since the survival rate of 22RV1 and LNCaP cells did not decrease linearly with increasing PTX concentration, it is difficult to estimate accurate IC50; therefore, only IC50 values for PTX in PC‑3 cells were given. When treating the cells with 5 mM MET, the IC50 of PTX decreased to 5.423±0.734 nM for PC‑3 cells. Annexin V and propidium iodide staining was used to investigate apoptosis by flow cytometry. The apoptotic mechanisms of MET + PTX in PCa were investigated by detecting the expression of apoptosis‑related proteins, activities of caspase‑3/7, intracellular ROS accumulation, mitochondrial membrane potential, and intracellular levels of adenosine 5'‑triphosphate (ATP). MET + PTX induced PCa apoptosis and ROS accumulation, and decreased mitochondrial membrane potential and intracellular levels of ATP. Taken together, these results indicated that MET + PTX suppressed PCa cell proliferation in a dose‑ and time‑dependent manner. In addition, MET + PTX induced apoptosis by increasing ROS levels, reducing mitochondrial membrane potential, and activating mitochondrial‑dependent apoptotic pathways.
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May-2019
Volume 17 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhao Y, Zeng X, Tang H, Ye D and Liu J: Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway. Oncol Lett 17: 4277-4284, 2019
APA
Zhao, Y., Zeng, X., Tang, H., Ye, D., & Liu, J. (2019). Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway. Oncology Letters, 17, 4277-4284. https://doi.org/10.3892/ol.2019.10119
MLA
Zhao, Y., Zeng, X., Tang, H., Ye, D., Liu, J."Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway". Oncology Letters 17.5 (2019): 4277-4284.
Chicago
Zhao, Y., Zeng, X., Tang, H., Ye, D., Liu, J."Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway". Oncology Letters 17, no. 5 (2019): 4277-4284. https://doi.org/10.3892/ol.2019.10119