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Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis
Published on: June 14, 2019
Canadine inhibits epithelial mesenchymal transformation of HPV-negative cervical cancer
Yan Ma, Qian-Qian Yang1, Dong-Mei Gu1
1Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
Abstract:
Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.
Insights
Canadine effectively inhibits cervical cancer progression by blocking epithelial-mesenchymal transition (EMT). This natural compound targets MAGEA3, offering a potential new therapeutic strategy for HPV-negative cervical cancers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cervical cancer treatment remains critical, even with HPV vaccination, necessitating research into HPV-negative cases.
- Epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis.
Purpose of the Study:
- To investigate the effect of Canadine on inhibiting EMT in cervical cancer.
- To explore the molecular mechanism underlying Canadine's action, focusing on MAGEA3.
Main Methods:
- Utilized immunoblotting, wound healing, and tumor invasion assays with HT-3 cells (HPV-negative).
- Analyzed gene expression data from the GEO database.
- Employed small interfering RNA (siRNA) and overexpression plasmids for MAGEA3 manipulation.
Main Results:
- Canadine inhibited EMT, proliferation, and migration of HT-3 cells.
- Canadine reduced the expression of MAGEA3 and other cervical tumor-associated genes.
- Decreasing MAGEA3 levels phenocopied Canadine's effects, while MAGEA3 overexpression counteracted Canadine's inhibition of EMT.
Conclusions:
- Canadine inhibits EMT in cervical cancer by targeting and reducing MAGEA3 expression.
- Canadine presents a potential therapeutic agent for cervical cancer, particularly HPV-negative types.
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