المؤلفون: Rashmi Bagga, Radhika Srinivasan, Shalmoli Bhattacharyya, Shifa Javed

المصدر: Molecular and Cellular Biochemistry. 473:51-62

مصطلحات موضوعية: 0301 basic medicine, Epithelial-Mesenchymal Transition, medicine.medical_treatment, Clinical Biochemistry, Cell, Uterine Cervical Neoplasms, Biology, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Cell Line, Tumor, Gene expression, medicine, Humans, Insulin-Like Growth Factor I, Molecular Biology, Cisplatin, Cervical cancer, Growth factor, Cell Biology, General Medicine, medicine.disease, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, Apoptosis, Cell culture, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, Female, Signal Transduction, medicine.drug

الوصف: Cancer stem cells (CSC) drive tumour progression and are implicated in relapse and resistance to conventional cancer therapies. Identification of differentially expressed genes by gene expression (GEP) profiling may help identify the differentially activated signalling pathways in cancer stem cells as opposed to bulk tumour cells which will provide new insights into cancer stem cell biology and aid in identification of novel therapeutic targets. Our study focused on the inhibition of CSC from cervical cancer cell lines by targeting insulin-like growth factor (IGF), which was identified by differential GEP. Targeted inhibition of IGF-1 by JB-1 trifluoroacetate (inhibitor of IGF) was carried out in SiHa, RSBS-14 and RSBS-43 cervical cancer derived cell lines. Effect of cisplatin was also evaluated. Inhibition of IGF-1 signalling was confirmed by demonstration of reduction in p-Akt levels. The cell biological effects of IGF-1 inhibition included an increase in G2M/S fraction, increased apoptosis and decreased invasive ability. JB-1 and cisplatin showed synergism. However, transcript levels of stemness and EMT markers showed variable levels following IGF inhibition. Overall, this proof-of-concept study has shown that IGF-1 is an attractive target for inhibition of CSC in invasive cervical cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::619fe4a597bb20186cf48bf314ac728cTest
https://doi.org/10.1007/s11010-020-03807-6Test

المؤلفون: Rashmi Bagga, Sanjeev Sharma, Shifa Javed, Bal Krishan Sharma, Swati Sood, Shalmoli Bhattacharyya, Lakhbir Kaur Dhaliwal, Radhika Srinivasan, Charan Singh Rayat

المصدر: BMC Cancer
BMC Cancer, Vol 18, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: 0301 basic medicine, HPV16, Cancer Research, Epithelial-Mesenchymal Transition, Biopsy, Population, Karyotype, Uterine Cervical Neoplasms, Antineoplastic Agents, Minisatellite Repeats, Biology, Low passage, lcsh:RC254-282, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Cell Line, Tumor, Genetics, medicine, Humans, Epithelial–mesenchymal transition, AC133 Antigen, CD133, Cell Self Renewal, education, Cervical cancer, education.field_of_study, Human papillomavirus 16, medicine.diagnostic_test, Cancer stem cells, Cell Cycle, Papillomavirus Infections, Cell cycle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Flow Cytometry, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer research, Neoplastic Stem Cells, Adenocarcinoma, Cell lines, Female, Cisplatin, Research Article

الوصف: Background Cervical cancer is a major cause of cancer-related mortality in women in the developing world. Cancer Stem cells (CSC) have been implicated in treatment resistance and metastases development; hence understanding their significance is important. Methods Primary culture from tissue biopsies of invasive cervical cancer and serial passaging was performed for establishing cell lines. Variable Number Tandem Repeat (VNTR) assay was performed for comparison of cell lines with their parental tissue. Tumorsphere and Aldefluor assays enabled isolation of cancer stem cells (CSC); immunofluorescence and flow cytometry were performed for their surface phenotypic expression in cell lines and in 28 tissue samples. Quantitative real-time PCR for stemness and epithelial-mesenchymal transition (EMT) markers, MTT cytotoxicity assay, cell cycle analysis and cell kinetic studies were performed. Results Four low-passage novel cell lines designated RSBS-9, − 14 and − 23 from squamous cell carcinoma and RSBS-43 from adenocarcinoma of the uterine cervix were established. All were HPV16+. VNTR assay confirmed their uniqueness and derivation from respective parental tissue. CSC isolated from these cell lines showed CD133+ phenotype. In tissue samples of untreated invasive cervical cancer, CD133+ CSCs ranged from 1.3–23% of the total population which increased 2.8-fold in radiation-resistant cases. Comparison of CD133+ with CD133− bulk population cells revealed increased tumorsphere formation and upregulation of stemness and epithelial-mesenchymal transition (EMT) markers with no significant difference in cisplatin sensitivity. Conclusion Low-passage cell lines developed would serve as models for studying tumor biology. Cancer Stem Cells in cervical cancer display CD133+ phenotype and are increased in relapsed cases and hence should be targeted for achieving remission. Electronic supplementary material The online version of this article (10.1186/s12885-018-4237-5) contains supplementary material, which is available to authorized users.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::881722c58dca4a1e2f1ff97c4464c018Test
https://pubmed.ncbi.nlm.nih.gov/29609538Test