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The Antitumor Efficiency of Zinc Finger Nuclease Combined with Cisplatin and Trichostatin A in Cervical Cancer Cells
- Source :
- Anti-Cancer Agents in Medicinal Chemistry. 20:2125-2135
- Publication Year :
- 2020
- Publisher :
- Bentham Science Publishers Ltd., 2020.
-
Abstract
- 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.
- Subjects :
- Cancer Research
Mice, Nude
Uterine Cervical Neoplasms
Antineoplastic Agents
Apoptosis
Hydroxamic Acids
Flow cytometry
HeLa
Mice
Structure-Activity Relationship
03 medical and health sciences
0302 clinical medicine
Western blot
Tumor Cells, Cultured
medicine
Animals
Humans
Viability assay
Cell Proliferation
030304 developmental biology
Pharmacology
Cisplatin
Mice, Inbred BALB C
0303 health sciences
Dose-Response Relationship, Drug
Molecular Structure
medicine.diagnostic_test
biology
Chemistry
Neoplasms, Experimental
biology.organism_classification
Zinc finger nuclease
Zinc Finger Nucleases
Trichostatin A
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Drug Therapy, Combination
Female
Drug Screening Assays, Antitumor
medicine.drug
Subjects
Details
- ISSN :
- 18715206
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Anti-Cancer Agents in Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....55f19dc5311492e4c24af3526539c25a
- Full Text :
- https://doi.org/10.2174/1871520620666200804102300