title: The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression.
abstract: Cervical cancer is a cause of cancer death, making it as the one of the most common cause for death among women globally. Though many studies before have explored a lot for cervical cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. We loaded gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles to cervical cancer cells due to the propertities of quercetin in ameliorating cellular processes and the easier absorbance of nanoparticles. Here, in our study, quercetin nanoparticles (NQ) were administrated to cells to investigate the underlying mechanism by which the cervical cancer was regulated. First, JAK2-inhibited carvical cancer cell lines were involved for our experiments in vitro and in vivo. Western blotting, quantitative RT-PCR (qRT-PCR), ELISA, Immunohistochemistry, and flow-cytometric analysis were used to determine the key signaling pathway regulated by JAK2 for cervical cancer progression. And the role of quercetin nanoparticles was determined during the process. Data here indicated that JAK2, indeed, expressed highly in cancer cell lines compared to the normal cervical cells. And apoptosis and autophagy were found in JAK2-inhibited cancer cells through activating Caspase-3, and suppressing Cyclin-D1 and mTOR regulated by Signal Transducer and Activator of Transcription (STAT) 3/5 and phosphatidylinositide 3-kinase/protein kinases (PI3K/AKT) signaling pathway. The cervical cancer cells proliferation was inhibited. Further, tumor size and weight were reduced by inhibition of JAK2 in vivo experiments. Notably, administration with quercetin nanoparticles displayed similar role with JAK2 suppression, which could inhibit cervical cancer cells proliferation, invasion and migration. In addition, autophogy and apoptosis were induced, promoting cervical cancer cell death. To our knowledge, it was the first time to evaluate the role of quercetin nanoparticles in improving cervical cancer from apoptosis, autophagy and proliferation, which could be a potential target for future therapeutic approach clinically.
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968, USA.
authors.forename: Cheng-Lin
authors.initials: CL
authors.lastname: Luo
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, NO.1 JiansheDong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Yu-Qiong
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan 450001, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan 450001, PR China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Song
authors.affiliation: College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan 450001, PR China.
authors.forename: Kai-Juan
authors.initials: KJ
authors.lastname: Wang
authors.affiliation: College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan 450001, PR China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Dai
authors.affiliation: College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan 450001, PR China. Electronic address: zhangjianying450052@139.com.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: College of Public Health, Zhengzhou University, No.100 Kexue Avenue, Zhengzhou, Henan 450001, PR China. Electronic address: yehua450052@139.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D011794:Quercetin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Cell death; Cervical cancer; JAK2; Proliferation; Quercetin nanoparticles