Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells

Baoleri,Xilin; Dong,Chao; Zhou,Yang; Zhang,Zhaojun; Lu,Xueliang; Xie,Pengming; Li,Yongqi

doi:10.3892/mmr.2015.4127

Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells

Authors:
- Xilin Baoleri
- Chao Dong
- Yang Zhou
- Zhaojun Zhang
- Xueliang Lu
- Pengming Xie
- Yongqi Li
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Affiliations: Department of Bone, International Mongolia Hospital of Inner Mongolia, Huhehot, Inner Mongolia 010020, P.R. China, Department of Bone and Soft Tissue Tumors, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China
Published online on: July 28, 2015 https://doi.org/10.3892/mmr.2015.4127
Pages: 5924-5932

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Abstract

The current study aimed to investigate the function of L-gossypol and low‑concentration doxorubicin (LCD) in the apoptosis of SW982 human synovial sarcoma cells (HSSCs). Wright‑Giemsa staining, Hoechst 33258 staining and transmission electron microscopy were used to identify cellular morphological alterations. In addition, an MTT assay was performed to measure the inhibitory rate of the drug, flow cytometry was used to detect alterations in apoptosis and the cell cycle, and western blot analysis was used to detect Bcl‑2 and Bax protein expression levels. Furthermore, the activity levels of caspase‑3 and ‑9 were measured in apoptotic cells. Following combination therapy, significant alterations in cellular morphology were observed, including condensation of the nucleus and formation of apoptotic bodies. Cell growth was demonstrated to be inhibited significantly in a dose‑ and time‑dependent manner. Flow cytometry results indicated that L‑gossypol administration resulted in G1 phase arrest, whereas doxorubicin led to S phase arrest. Combination therapy resulted in a significant increase in the number of S phase‑arrested cells. Following treatment with the drugs, Bcl‑2 protein levels were observed to be reduced whilst Bax levels increased, and significant caspase‑3 and ‑9 activation was observed during combination therapy. Combination therapy with L‑gossypol and LCD inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone. It was hypothesized that these effects are mediated via downregulation of the Bcl-2 protein and upregulation of Bax protein.

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