Recombinant oncolytic adenovirus H101 combined with siBCL2: cytotoxic effect on uveal melanoma cell lines
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Updated: May 20, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Xiaolin Huang1, Renbing Jia, Xiaoping Zhao
1Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, PR China.
Background:
Deregulation of Bcl2 pathway is implicated in the pathogenesis of uveal melanoma (UM). Oncolytic adenovirus H101 is the world's first oncolytic viral therapy for cancer approved for clinical use. We aimed to explore a potential synergy of downregulating Bcl2 pathway using a small interfering RNA (siBCL2) combined with H101 therapy on UM cell lines.
Methods:
The sensitivity to adenovirus infection was analysed by flow cytometry. PCR, real-time-PCR and western blot were used to detect Bcl2, p53, Bax and fibre expression. Appropriate multiplicity of H101 infection and cell survival rate were measured by a cell counting kit-8 assay. UM cells were stained with Annexin-V and propidium iodide for apoptosis assay and cell cycle distribution.
Results:
VUP cells (without elevation of Bcl2) exhibited greater sensitivity to adenovirus infection than OM431 cells (Bcl2 elevated cell line). Bcl2 expression was markedly reduced by siBCL2 or siBCL2 plus H101. Combined treatment with siBCL2 and H101 produced substantial growth inhibition of OM431 cells by enhancing apoptosis and cell cycle arrest through Bax-p53-induced apoptotic pathway.
Conclusions:
SiBCL2 and H101 exhibited synergistic cytotoxic effect in Bcl2 elevated UM cell lines and could potentially serve as a novel targeted molecular therapy for UM.
Insights
Combining small interfering RNA for Bcl2 (siBCL2) with oncolytic adenovirus H101 shows synergistic effects against uveal melanoma (UM). This novel therapy enhances apoptosis and cell cycle arrest in UM cells with elevated Bcl2, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Bcl2 pathway deregulation is key in uveal melanoma (UM) pathogenesis.
- Oncolytic adenovirus H101 is a clinically approved viral therapy for cancer.
- Investigating combined siBCL2 and H101 therapy for UM is warranted.
Purpose of the Study:
- To explore the synergistic potential of downregulating the Bcl2 pathway with siBCL2 combined with H101 therapy in UM cell lines.
- To assess the impact of this combination on UM cell growth, apoptosis, and cell cycle.
Main Methods:
- Adenovirus infection sensitivity was analyzed via flow cytometry.
- Gene and protein expression (Bcl2, p53, Bax, fiber) were quantified using PCR and Western blot.
- Cell viability, apoptosis, and cell cycle distribution were assessed using CCK-8, Annexin-V, and propidium iodide staining.
Main Results:
- UM cells with elevated Bcl2 (OM431) were less sensitive to H101 than those without (VUP).
- siBCL2 significantly reduced Bcl2 expression, with or without H101.
- Combined siBCL2 and H101 treatment strongly inhibited OM431 cell growth by promoting apoptosis and cell cycle arrest via the Bax-p53 pathway.
Conclusions:
- siBCL2 and H101 demonstrate a synergistic cytotoxic effect in Bcl2-elevated UM cell lines.
- This combination therapy presents a promising novel targeted molecular approach for UM treatment.
