Insulin growth factor-1 pathway in cervical carcinoma cancer stem cells
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Insulin growth factor‑1 pathway in cervical carcinoma cancer stem cells Shifa Javed1 · Shalmoli Bhattacharyya2 · Rashmi Bagga3 · Radhika Srinivasan1 Received: 7 April 2020 / Accepted: 18 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords IGF-1 · CD133 · ALDH1 · Cancer stem cells · Epithelial-mesenchymal transition · Cervical cancer
Introduction Cervical cancer is the fourth most common cancer in women world-wide [1] with a relatively high cancer-related mortality in developing countries due to advanced stage at presentation. The standard of care for these patients is chemoradiation. Radiation therapy, like chemotherapy, results in cell death by apoptosis and necrosis. Whereas most cells in a tumour population are sensitive to such treatments, the Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03807-6) contains supplementary material, which is available to authorized users. * Radhika Srinivasan [email protected] 1
Molecular Pathology Laboratory, Department of Cytology & Gynec. Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh PIN‑160023, India
2
Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3
Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
cancer stem cells or CSC residing within a tumour are relatively resistant, so survive the treatment and are responsible for recurrence of cancer. Indeed, this hypothesis is one of the several models of radiation-resistance and relapse in tumours [2]. Hence, a better understanding of CSC in cervical cancer in ter
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