Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells

Ding,Feng; Liu,Tianfeng; Yu,Nina; Li,Shihong; Zhang,Xiaofei; Zheng,Guanghong; Lv,Chunming; Mou,Kai; Xu,Jia; Li,Bo; Wang,Surong; Song,Haibo

doi:10.3892/mmr.2016.5577

Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells

Authors:
- Feng Ding
- Tianfeng Liu
- Nina Yu
- Shihong Li
- Xiaofei Zhang
- Guanghong Zheng
- Chunming Lv
- Kai Mou
- Jia Xu
- Bo Li
- Surong Wang
- Haibo Song
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Affiliations: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China, Department of Cardiology, Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China
Published online on: July 29, 2016 https://doi.org/10.3892/mmr.2016.5577
Pages: 2853-2859

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Abstract

Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor. However, to the best of our knowledge there is no previous evidence of NC involvement in the apoptosis or proliferation of ovarian cancer cells and the underlying molecular mechanisms. The present study aimed to investigate the influence of NC on the viability and apoptosis of ovarian cancer cells and the synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The viability and proliferation of ovarian cancer cells were examined using a methyl thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic rate of ovarian cancer cells was detected by flow cytometry. The expression of apoptosis‑associated proteins and Akt serine/threonine kinase 1 (Akt) were determined by western blot analysis following NC treatment. The inhibitory effect of NC on the proliferation of ovarian cancer cells was demonstrated in a time and dose‑dependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was also observed. It was determined that NC significantly downregulated the protein expression levels of B‑cell CLL/lymphoma 2 (Bcl-2) and upregulated the expression of Bcl‑2‑associated X protein, p53, caspase‑3 and ‑9. NC suppressed Akt phosphorylation. Additionally, the present study demonstrated that the effect of NC on the proliferation and apoptosis of ovarian cancer cells was Akt‑dependent by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the viability of ovarian cancer cells when combined with DOX. The current study demonstrated that NC inhibited the proliferation and induced the apoptosis of ovarian cancer cells via the Akt signaling pathway and highlighted its potential clinical application for the treatment of ovarian cancer.

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