title: Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells.
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.
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Nina
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Lv
authors.affiliation: Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Mou
authors.affiliation: Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
authors.forename: Surong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Song
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053119:Benzophenanthridines / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D053119:Benzophenanthridines; D004317:Doxorubicin; C013615:nitidine; D051057:Proto-Oncogene Proteins c-akt