MicroRNA-143 Sensitizes Cervical Cancer Cells to Cisplatin: a Promising Anticancer Combination Therapy

Author(s):  
Yalda Baghay Esfandyari ◽  
Mohammad Amin Doustvandi ◽  
Mohammad Amini ◽  
Behzad Baradaran ◽  
Sheyda Jodeiry Zaer ◽  
...  
2021 ◽  
Vol 21 ◽  
Author(s):  
Yixin Duan ◽  
Haixia Bai ◽  
Xiang Li ◽  
Depu Wang ◽  
Yin Wang ◽  
...  

Background: : A major challenge in cervical cancer radiotherapy is to tailor the radiation doses efficiently to both eliminate malignant cells and to reduce the side effects to normal tissue. Oncolytic adenoviral drug H101 is recently tested and approved for topical adjuvant treatment of several malignancies. Objective: This study is to evaluate the potential neoadjuvant radiotherapy benefits of H101 by testing the inhibitory function of H101 combined with radiation in different cervical cancer cells. Methods: Human cervical cancer cells C33a, SiHa, CaSki, and Hela were treated with varying concentrations of H101 alone or combined with radiation (2Gy or 4Gy). Cell viability and apoptosis were measured at indicated time intervals. HPV16 E6 and cellular p53 mRNA expression alteration were measured by qRT-PCR. RNA scope in-situ detect HPV E6 status. P53 protein alteration are detected by Western blot. Results: Cell viability and apoptosis show the combination of a high dose of H101 (MOI=1000, 10000) with radiation yielded a synergistic anti-cancer effect in all tested cervical cancer cell lines (P<0.05), with the greatest effect achieved in HPV negative C33a cells (P<0.05). Low HPV16 viral load SiHa cell was more sensitive to combination therapy than high HPV16 viral load CaSki cell (P<0.05). The combined treatment could reduce HPV16 E6 expression and increase cellular P53 level compared to radiation alone in SiHa and CaSki (P<0.05). Conclusions: Oncolytic adenoviral H101 effectively enhances the antitumor efficacy of radiation in cervical cancer cells and may serve as a novel combination therapy for cervical cancer.


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.


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