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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
XIAP underlies apoptosis resistance of renal cell carcinoma cells
Wen Zheng Yang1, Haijiang Zhou2, Yong Yan3
1Department of Anesthesiology, Beijing Shijitan Hospital, Beijing 100038, P.R. China.
Abstract:
X‑linked inhibitor of apoptosis (XIAP), a key member of the inhibitors of apoptosis protein family, can inhibit apoptosis by directly binding to the initiator caspase‑9, ‑3 and ‑7, thereby promoting tumor cell survival during tumor progression. In the present study, XIAP basal expression levels were investigated and its contribution to the resistance to apoptosis was evaluated, in the RCC cell lines exposed to apoptosis‑inducing drugs. This was investigated by histological methods and western blot analysis. Using RNA interference, elimination of XIAP in Caki‑1 cells was also studied, and its contribution to the sensitivity to apoptosis induced through the intrinsic pathway was observed. Differences in XIAP expression were detected between ClearCa‑2 and ClearCa‑6 cell lines. ClearCa‑6 cells with lower expression of XIAP were more sensitive to apoptosis‑inducing drugs, compared with ClearCa‑2 cells. However, the levels of XIAP expression in both cell lines were stable during apoptosis. Furthermore, a Caki‑1 cell line with no XIAP expression was used, and was demonstrated to be more sensitive to the apoptosis induced by the mitochondrial pathway. These results suggested that downregulation of XIAP expression could enhance the sensitivity of RCC cells to apoptosis, and the basal expression of XIAP during apoptosis is stable. This may provide novel insight for targeted gene therapy against XIAP, in the clinic.
Insights
Downregulating X-linked inhibitor of apoptosis (XIAP) enhances kidney cancer cell sensitivity to apoptosis. XIAP expression remains stable during apoptosis, offering potential for targeted gene therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- X-linked inhibitor of apoptosis (XIAP) is a key protein that inhibits apoptosis, promoting tumor cell survival.
- Understanding XIAP's role in renal cell carcinoma (RCC) is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate XIAP basal expression levels in RCC cell lines.
- To evaluate XIAP's contribution to apoptosis resistance in RCC cells treated with apoptosis-inducing drugs.
- To assess the impact of XIAP elimination on apoptosis sensitivity in RCC cells.
Main Methods:
- Histological methods and Western blot analysis were used to determine XIAP expression.
- RNA interference was employed to eliminate XIAP in Caki-1 cells.
- Apoptosis sensitivity was measured in RCC cell lines with varying XIAP levels.
Main Results:
- ClearCa-6 cells with lower XIAP expression showed increased sensitivity to apoptosis-inducing drugs compared to ClearCa-2 cells.
- XIAP expression levels remained stable in both cell lines during apoptosis.
- Caki-1 cells lacking XIAP expression exhibited heightened sensitivity to apoptosis induced via the mitochondrial pathway.
Conclusions:
- Downregulation of XIAP expression can significantly enhance the sensitivity of RCC cells to apoptosis.
- Basal XIAP expression is stable throughout the apoptotic process.
- Targeting XIAP presents a promising strategy for novel gene therapy in clinical oncology.
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