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[Antisense oligonucleotides targeting XIAP induce apoptosis and enhance radiotherapeutic activity against hep-2 cells
Qian Hao1, Xiaoming Li, Xiuying Lu
1Department of Otolaryngology-Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, 050082, China.
Objective:
To investigate the down-regulation effect of antisense oligonucleotides (AS ODNs) targeting X-chromosome-linked inhibitors of apoptosis (XIAP) on hep-2 cells apoptosis and radiotherapy sensitivity in vitro.
Method:
G4 AS ODN was transfected into cultured hep-2 cells which received radiation 6 hours later. Twenty-four hours after radiation, cells were observed under inverted phase contrast microscope and fluorescence microscope. Apoptosis rate, cell viability, expression of XIAP mRNA and protein were tested.
Result:
In cultured hep-2 cells, G4 AS ODN down-regulated XIAP mRNA expression. Furthermore, the protein expression of XIAP and the cell viability decreased too. In contrast to that, the scrambled control ODN caused minor XIAP loss and less cell inhibition. In addition, G4 AS ODNs activated Hep-2 cells after the radiation of 4 Gy Co60 ray.
Conclusion:
XIAP is a viable target for cancer therapy in human laryngeal neoplasms. In cultured Hep-2 cells, AS ODN targeting XIAP can down-regulate protein expression of XIAP, induce cell apoptosis and enhance the radiotherapy sensitivity.
Insights
Antisense oligonucleotides (AS ODNs) targeting X-chromosome-linked inhibitors of apoptosis (XIAP) effectively reduce XIAP expression in laryngeal cancer cells. This approach enhances apoptosis and improves radiotherapy sensitivity in vitro.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Context:
- Laryngeal neoplasms present a significant challenge in cancer therapy.
- X-chromosome-linked inhibitor of apoptosis (XIAP) is implicated in cancer cell survival and radioresistance.
- Developing novel therapeutic strategies to enhance radiotherapy efficacy is crucial.
Purpose:
- To investigate the efficacy of antisense oligonucleotides (AS ODNs) targeting XIAP in down-regulating XIAP expression.
- To evaluate the impact of XIAP down-regulation on hep-2 cell apoptosis.
- To determine the effect of XIAP-targeting AS ODNs on radiotherapy sensitivity in vitro.
Summary:
- G4 AS ODN transfection in hep-2 cells led to significant down-regulation of XIAP mRNA and protein expression.
- The treatment resulted in decreased cell viability and induced apoptosis in hep-2 cells.
- Compared to scrambled control ODN, G4 AS ODN demonstrated enhanced induction of apoptosis and reduced cell viability, particularly after radiotherapy.
Impact:
- XIAP represents a promising therapeutic target for human laryngeal neoplasms.
- AS ODNs targeting XIAP demonstrate potential in sensitizing cancer cells to radiotherapy.
- This study provides a basis for further investigation of AS ODN-based therapies in combination with radiation for laryngeal cancer treatment.
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