Near‐infrared emissive polymer coated IR ‐820 nanoparticles assisted photo‐thermal therapy for cervical cancer cells

Author(s):  
Lijun Zhu ◽  
Jianjun Chen ◽  
Ting Yan ◽  
Alimu Gulinigaer ◽  
Xueliang Zhang ◽  
...  
2020 ◽  
Vol 20 ◽  
Author(s):  
Wenhuan Wang ◽  
Xiaochun Tan ◽  
Jie Jiang ◽  
Yiqi Cai ◽  
Fangfang Feng ◽  
...  

Background: High risk type 16 of human papillomavirus (HPV16) is associated with 50% of cervical cancer, for which reliable targeted therapies are lacking. HPV early protein 7 (E7) is an oncoprotein responsible for cell malignant transformation. In our previous work, a highly specific affibody targeting HPV16E7 (ZHPV16E7) was developed. Objective: In order to improve the targeted therapeutic effect, the present study prepared an affitoxin consisting of ZHPV16E7 fused with granzyme B (GrB), namely, ZHPV16E7-GrB, and evaluated its targeting action in vitro and in vivo. Methods: The ZHPV16E7-GrB fusion protein was produced in a prokaryotic expression system. The targeted binding properties of the ZHPV16E7-GrB to the HPV16E7 were confirmed by immunofluorescence assay (IFA) in cervical cancer cell lines, by immunohistochemical assay (IHA) in cervical cancer tissue from clinical specimens and by near-infrared imaging in tumour-bearing mice. The anti-tumour effect on both cervical cancer cells in vitro and tumour-bearing mice in vivo were further evaluated. Results: A 34-kDa ZHPV16E7-GrB fusion protein was produced in E. coli and displayed corresponding immunoreactivity. IFA revealed that ZHPV16E7-GrB bound specifically to HPV16-positive TC-1 and SiHa cells. IHA showed that ZHPV16E7-GrB also bound specifically to HPV16-positive clinical tissue specimens. In addition, the near-infrared imaging results showed that ZHPV16E7-GrB was enriched in tumour tissues. Moreover, both the ZHPV16E7-GrB affitoxin and ZHPV16E7 affibody (without GrB) significantly reduced the proliferation of cervical cancer cells in vitro and tumour-bearing mice in vivo, and the antiproliferative effect of ZHPV16E7-GrB was higher than that of the ZHPV16E7 affibody. Conclusions: The affitoxin by coupling the affibody with GrB is a promising targeted therapeutic agent with the dual advantages of the targeted affibody and the GrB cytotoxin.


2020 ◽  
Vol 56 (65) ◽  
pp. 9332-9335
Author(s):  
Sandra Estalayo-Adrián ◽  
Salvador Blasco ◽  
Sandra A. Bright ◽  
Gavin J. McManus ◽  
Guillermo Orellana ◽  
...  

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.


2020 ◽  
Vol 20 (17) ◽  
pp. 2125-2135
Author(s):  
Ci Ren ◽  
Chun Gao ◽  
Xiaomin Li ◽  
Jinfeng Xiong ◽  
Hui Shen ◽  
...  

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.


2018 ◽  
Vol 18 (3) ◽  
pp. 412-421 ◽  
Author(s):  
Madhumitha Kedhari Sundaram ◽  
Mohammad Zeeshan Ansari ◽  
Abdullah Al Mutery ◽  
Maryam Ashraf ◽  
Reem Nasab ◽  
...  

Introduction: Epidemiological studies indicate that diet rich in fruits and vegetables is associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein’s role as a natural epigenetic modifier in human cervical cancer cells, HeLa. Methods: Expression of the tumour suppressor genes (TSGs) [MGMT, RARβ, p21, E-cadherin, DAPK1] as well the methylation status of their promoters were examined alongwith the activity levels of DNMT and HDAC enzymes after treatment with genistein. Expression of DNMTs and HDACs was also studied. In-silico studies were performed to determine the interaction of genistein with DNMTs and HDACs. Results: Genistein treatment significantly reduced the expression and enzymatic activity of both DNMTs and HDACs in a time-dependent way. Molecular modeling data suggest that genistein can interact with various members of DNMT and HDAC families and support genistein mediated inhibition of their activity. Timedependent exposure of genistein reversed the promoter region methylation of the TSGs and re-established their expression. Conclusions: In this study, we find that genistein is able to reinstate the expression of the TSGs studied by inhibiting the action of DNMTs and HDACs. This shows that genistein could be an important arsenal in the development of epigenetic based cancer therapy.


2020 ◽  
Vol 19 ◽  
pp. 153303382093413 ◽  
Author(s):  
Huiling Zhang ◽  
Ruxin Chen ◽  
Jinyan Shao

Purpose: The current study was intended to research the functional role and regulatory mechanism of microRNA-96-5p in the progression of cervical cancer. Methods: MicroRNA-96-5p expression in cervical cancer tissues was assessed by quantitative real-time polymerase chain reaction. The association between microRNA-96-5p expression and clinicopathological features of patients with cervical cancer was analyzed. MTT, flow cytometry, wound healing, and transwell assay were performed to evaluate the viability, apoptosis, migration, and invasion of Hela and SiHa cells. Targetscan, dual-luciferase reporter gene assay, and RNA pull-down analysis were constructed to evaluate the target relationship between microRNA-96-5p and secreted frizzled-related protein 4. Results: MicroRNA-96-5p was overexpressed in cervical cancer tissues, and microRNA-96-5p expression was markedly associated with the clinical stage and lymph node metastasis of patients with cervical cancer. Overexpressed microRNA-96-5p facilitated the viability, migration, invasion, and inhibited the apoptosis of Hela and SiHa cells, whereas suppression of microRNA-96-5p exerted the opposite trend. Secreted frizzled-related protein 4 was proved to be a target of microRNA-96-5p. Silencing of secreted frizzled-related protein 4 eliminated the anti-tumor effect of microRNA-96-5p on cervical cancer cells. Conclusions: MicroRNA-96-5p facilitated the viability, migration, and invasion and inhibited the apoptosis of cervical cancer cells via negatively regulating secreted frizzled-related protein 4.


RSC Advances ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 5021-5021
Author(s):  
Laura Fisher

Retraction of ‘Down-regulation of the radiation-induced pEGFRThr654 mediated activation of DNA-PK by Cetuximab in cervical cancer cells’ by Yunxiang Qi et al., RSC Adv., 2020, 10, 1132–1141, DOI: 10.1039/C9RA04962B.


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