Javed Shifa, Bhattacharyya Shalmoli, Bagga Rashmi, Srinivasan Radhika
Molecular Pathology Laboratory, Department of Cytology & Gynec. Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, PIN-160023, India.
Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Mol Cell Biochem. 2020 Oct;473(1-2):51-62. doi: 10.1007/s11010-020-03807-6. Epub 2020 Jun 29.
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.
癌症干细胞（CSC）驱动肿瘤进展，并与传统癌症治疗的复发和耐药性有关。通过基因表达（GEP）谱分析鉴定差异表达基因，可能有助于识别癌症干细胞中与大量肿瘤细胞相比差异激活的信号通路，这将为癌症干细胞生物学提供新的见解，并有助于识别新的治疗靶点。我们的研究聚焦于通过靶向胰岛素样生长因子（IGF）来抑制宫颈癌细胞系中的CSC，IGF是通过差异GEP鉴定出来的。在SiHa、RSBS-14和RSBS-43宫颈癌衍生细胞系中，使用JB-1三氟乙酸盐（IGF抑制剂）对IGF-1进行靶向抑制。同时也评估了顺铂的作用。通过证明p-Akt水平降低来确认IGF-1信号传导的抑制。IGF-1抑制的细胞生物学效应包括G2M/S期比例增加、凋亡增加和侵袭能力降低。JB-1和顺铂显示出协同作用。然而，在IGF抑制后，干性和上皮-间质转化（EMT）标志物的转录水平显示出不同程度的变化。总体而言，这项概念验证研究表明，IGF-1是抑制浸润性宫颈癌中CSC的一个有吸引力的靶点。
