Smac mimetic compound LCL161 sensitizes esophageal carcinoma cells to radiotherapy by inhibiting the expression of inhibitor of apoptosis protein
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- 作者：Qin Qin (1)
Yun Zuo (2)
Xi Yang (1)
Jing Lu (1)
Liangliang Zhan (1)
Liping Xu (1)
Chi Zhang (1)
Hongcheng Zhu (1)
Jia Liu (1)
Zheming Liu (1)
Guangzhou Tao (3)
Shengbin Dai (4)
Xizhi Zhang (5)
Jianxin Ma (6)
Jing Cai (7)
Xinchen Sun (1) - 关键词：LCL161 ; IAP ; ESCC ; Radiosensitization ; Apoptosis
- 刊名：Tumor Biology
- 出版年：2014
- 出版时间：March 2014
- 年：2014
- 卷：35
- 期：3
- 页码：2565-2574
- 全文大小：3,674 KB
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Yun Zuo (2)
Xi Yang (1)
Jing Lu (1)
Liangliang Zhan (1)
Liping Xu (1)
Chi Zhang (1)
Hongcheng Zhu (1)
Jia Liu (1)
Zheming Liu (1)
Guangzhou Tao (3)
Shengbin Dai (4)
Xizhi Zhang (5)
Jianxin Ma (6)
Jing Cai (7)
Xinchen Sun (1)
1. Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
2. Department of Radiation Oncology, The No.1 People’s Hospital of Zhang Jiagang, Zhang Jiagang, China
3. Department of Radiation Oncology, The No.1 People’s Hospital of Huai’an, Huai’an, China
4. Department of Radiation Oncology, People’s Hospital of Tai Zhou, Taizhou, China
5. Department of Radiation Oncology, Subei People’s Hospital, Yangzhou, China
6. Department of Radiation Oncology, The No.2 People’s Hospital of Lian Yungang, Lianyungang, China
7. Nantong Tumor Hospital, Nantong, China - ISSN：1423-0380
文摘
Currently, unresectable esophageal squamous cell carcinoma (ESCC) is primarily treated by chemoradiotherapy. However, the outcome has not improved significantly due to radioresistance of cancer cells. This study aimed to determine the radiosensitizing effect of LCL161, a novel second mitochondrial-derived activator of caspase (Smac) mimetic, in ESCC cells. ESCC cell lines were treated with LCL161 or radiation, alone or in combination. Cell proliferation was detected by MTT assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis was detected by flow cytometry. The results showed that LCL161 potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.4-.0. LCL161 increased radiation-induced DNA double-stranded breaks and promoted the apoptosis of ESCC cells, which could be abrogated by a pan-caspase inhibitor z-VAD-FMK. Furthermore, LCL161 decreased the level of cIAP1 in ESCC cells in a dose-dependent manner and synthesized with irradiation to promote the activation of caspase 8 and the upregulation of TNFα expression in ESCC cells. In conclusion, LCL161 acts as a strong radiosensitizer in human esophageal cancer cells by inhibiting the expression of cIAP1 and promoting the activation of caspase 8, leading to enhanced apoptosis.