Lower back pain is a common concern, and 40% of all cases involve the degeneration of the intervertebral disc (IVD). However, the excessive apoptosis of disc cells plays an important role in IVD degeneration, particularly in the nucleus pulposus (NP). Thus, anti-apoptotic gene therapy to attenuate or reverse the degenerative process within the NP is being developed. Survivin is a unique inhibitor of apoptosis (IAP) and has been extensively investigated in cancer cells. However, little is known of the effects of survivin transfection on NP cells derived from degenerative human disc. In this study, we aimed to investigate the effects of lentivirus (LV)‑mediated survivin transfection on the morphology and apoptosis of NP cells derived from degenerative human disc in vitro. NP cells were transfected with LV‑mediated survivin. Subsequently, cell morphology was observed and the survivin mRNA expression levels were measured by RT‑qPCR. Apoptosis was analyzed by flow cytometry and by measuring caspase‑3 activity. The results revealed that the morphology of the NP cells derived from degenerative human disc transfected with LV‑mediated survivin was significantly altered as evidenced by cytomorphosis, the reduction of the cytoplasm and cell shrinkage. Following transfection, survivin gene expression significantly increased in the transfected cells and subsequent generation cells; however, no significant differences in the cell apoptotic rate and caspase‑3 activity were observed. We found that transfection of the survivin gene into NP cells led to the stable expression of survivin and induced marked changes in cell morphology. Furthermore, no significant anti-apoptotic effects were observed following LV‑mediated survivin transfection. Overall, our findings demonstrate that LV carrying surviving may be used to successfully enforce the expression of survivin in NP cells. However, cell morphology was evidently altered, whereas the apoptotic rate did not decrease. Comprehensive studies on the feasibility of using survivin in gene therapy in an aim to attenuate disc degeneration are warranted. Further research on the mechanisms responsible for the changes in cell morphology and cell function are also required.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494593PMC
http://dx.doi.org/10.3892/ijmm.2015.2225DOI Listing

Publication Analysis

Top Keywords

survivin transfection
16
cells derived
16
derived degenerative
16
degenerative human
16
human disc
16
lv‑mediated survivin
16
cell morphology
16
survivin
12
survivin gene
12
cells
11

Similar Publications

Oncolytic viral-based therapy and specific gene expression by promoters are modern targeted oncotherapy approaches that have gained significant attention in recent years. In this study, both strategies were combined by designing cancer-specific activation of vesicular stomatitis virus matrix expression under the survivin promoter. The matrix sequence was cloned downstream of the survivin promoter (pM).

View Article and Find Full Text PDF

Dual sgRNA-directed knockout gene expression using CRISPR/Cas9 technology for editing gene in triple-negative breast cancer.

Narra J

December 2024

Animal Research Facilities, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) offers a robust approach for genome manipulation, particularly in cancer therapy. Given its high expression in triple-negative breast cancer (TNBC), targeting with CRISPR/Cas9 holds promise as a therapeutic strategy. The aim of this study was to design specific single guide ribonucleic acid (sgRNA) for CRISPR/Cas9 to permanently knock out the gene, exploring its potential as a therapeutic approach in breast cancer while addressing potential off-target effects.

View Article and Find Full Text PDF

Elevated MRPS23 expression facilitates aggressive phenotypes in breast cancer cells.

Cell Mol Biol (Noisy-le-grand)

January 2025

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Mitochondrial ribosomal protein S23 (MRPS23), encoded by a nuclear gene, is a well-known driver of proliferation in cancer. It participates in mitochondrial protein translation, and its expression association has been explored in many types of cancer. However, MRPS23 expression associations are rarely reported in breast cancer (BC).

View Article and Find Full Text PDF

Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells.

Cancers (Basel)

November 2024

Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.

Small-cell lung cancer (SCLC) has a poor prognosis because it is often diagnosed after it has spread and develops multi-drug resistance. Epibrassinolide (EB) is a plant steroid hormone with widespread distribution and physiological effects. In plants, EB-activated gene expression occurs via a GSK-mediated signaling pathway, similar to β-catenin signaling in animal cells that is elevated in cancer cells.

View Article and Find Full Text PDF

The use of combinatorial siRNAs shows great promise for drug discovery, but the identification of safe and effective siRNA combinations remains challenging. Here, we develop a massively multiplexed technology for systematic screening of siRNA-based cocktail therapeutics. We employ composite micro-carriers that are responsive to near infrared light and magnetic field to achieve photoporation-facilitated siRNA transfection to individual cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!