08 April 2018 : Laboratory Research
Upregulation of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) Mediates the Reversal Effect of Verapamil on Chemo-Resistance to Adriamycin of Hepatocellular CarcinomaGuangshan Yang123ABCDEF, Gaofei Fan2BCDE, Tengyue Zhang2ABCDEF, Kelong Ma4ABCD, Jin Huang2BC, Miao Liu2AB, Xiaolu Teng2AB, Kun Xu2AB, Pingsheng Fan12ACDFG, Dongmiao Cheng5ACDFG
Med Sci Monit 2018; 24: LBR2072-2082
BACKGROUND: The aim of this study was to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in the reversal effect of verapamil (VER) on chemo-resistance to Adriamycin (ADM) in treatment of hepatocellular carcinoma (HCC).
MATERIAL AND METHODS: HCC cell lines SMMC-7721 and BEL-7402 were used as model cell lines. High-throughput transcriptome sequencing based on Illumina technology was used to screen whether UCHL1 mediated the reversal effect of VER on chemo-resistance. Quantitative real-time PCR (qRT-PCR) was performed to determine the expression level of UCHL1 mRNA in HCC cells, and western blot analysis was performed to examine the protein expression of UCHL1 protein in HCC cells. Immunohistochemistry assay was performed to determine the protein expression of UCHL1 in tissue samples from patients presenting with either positive or negative responses to the reversal therapeutic regimen of VER. Moreover, cell models with UCHL1 knockdown and overexpression were established to examine the reversal effect of VER on chemo-resistance to ADM in HCC cells. Cell apoptosis was determined by flow cytometry following Annexin V-PI staining.
RESULTS: The expression levels of UCHL1 genes correlated with the level of apoptosis induced by ADM+VER. Overexpression of UCHL1 genes promoted apoptosis in cells treated with VER+ADM. UCHL1 knockdown using siRNA weakened the effect of ADM+VER, indicating that ADM+VER promotes HCC cell apoptosis and that UCHL1 genes participate in VER-mediated promotion in tumor cell apoptosis.
CONCLUSIONS: Upregulation of UCHL1 enhanced the reversal effect of VER on chemo-resistance to ADM and promoted cell apoptosis. The underlying mechanism of the function of UCHL1 and the signaling pathway involved in its effect are to be investigated in our future research.
Keywords: Antineoplastic Combined Chemotherapy Protocols, Drug Resistance, Epirubicin, Ubiquitin Thiolesterase, Verapamil
01 May 2023 : EditorialEditorial: Twenty Years On from Sequencing the Human Genome, Personalized/Precision Oncology Prepares to Meet the Challenges of Checkpoint Inhibitor Therapy
Med Sci Monit 2023; 29:e940911
28 May 2023 : Database AnalysisScientometric and Visualized Analysis of Intravoxel Incoherent Motion Magnetic Resonance Imaging: 1988-2021
Med Sci Monit In Press; DOI: 10.12659/MSM.938715
25 May 2023 : Database AnalysisThe COVID-19 Crisis and the Incidence of Alcohol-Related Deaths in Poland
Med Sci Monit In Press; DOI: 10.12659/MSM.940904
25 May 2023 : Review articleA Review of Preclinical and Clinical Studies in Support of the Role of Non-Steroidal Anti-Inflammatory Drug...
Med Sci Monit In Press; DOI: 10.12659/MSM.940635
25 May 2023 : Clinical ResearchPeriapical Lesions and Missed Canals in Endodontically Treated Teeth: A Cone-Beam Computed Tomographic Stud...
Med Sci Monit In Press; DOI: 10.12659/MSM.940533
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : EditorialEditorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...
Med Sci Monit 2022; 28:e935952