A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities
Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates N...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2016-08-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://prod.karger.com/Article/FullText/447797 |
| _version_ | 1811195255419043840 |
|---|---|
| author | Youlin Deng Zhongliang Wang Fugui Zhang Min Qiao Zhengjian Yan Qiang Wei Jing Wang Hao Liu Jiaming Fan Yulong Zou Junyi Liao Xue Hu Liqun Chen Xinyi Yu Rex C. Haydon Hue H. Luu Hongbo Qi Tong-Chuan He Junhui Zhang |
| author_facet | Youlin Deng Zhongliang Wang Fugui Zhang Min Qiao Zhengjian Yan Qiang Wei Jing Wang Hao Liu Jiaming Fan Yulong Zou Junyi Liao Xue Hu Liqun Chen Xinyi Yu Rex C. Haydon Hue H. Luu Hongbo Qi Tong-Chuan He Junhui Zhang |
| author_sort | Youlin Deng |
| collection | DOAJ |
| description | Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer. |
| first_indexed | 2024-04-12T00:39:14Z |
| format | Article |
| id | doaj.art-1f94d4b38fe3473fa701feb223518027 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T00:39:14Z |
| publishDate | 2016-08-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-1f94d4b38fe3473fa701feb2235180272022-12-22T03:55:03ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-08-0139387188810.1159/000447797447797A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer ActivitiesYoulin DengZhongliang WangFugui ZhangMin QiaoZhengjian YanQiang WeiJing WangHao LiuJiaming FanYulong ZouJunyi LiaoXue HuLiqun ChenXinyi YuRex C. HaydonHue H. LuuHongbo QiTong-Chuan HeJunhui ZhangBackground/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.http://prod.karger.com/Article/FullText/447797Cancer pathwaysCell signalingSynergistic effectCancer therapyIGF signalingIGF-1ROvarian cancerDrug repurposingNiclosamide |
| spellingShingle | Youlin Deng Zhongliang Wang Fugui Zhang Min Qiao Zhengjian Yan Qiang Wei Jing Wang Hao Liu Jiaming Fan Yulong Zou Junyi Liao Xue Hu Liqun Chen Xinyi Yu Rex C. Haydon Hue H. Luu Hongbo Qi Tong-Chuan He Junhui Zhang A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities Cellular Physiology and Biochemistry Cancer pathways Cell signaling Synergistic effect Cancer therapy IGF signaling IGF-1R Ovarian cancer Drug repurposing Niclosamide |
| title | A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities |
| title_full | A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities |
| title_fullStr | A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities |
| title_full_unstemmed | A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities |
| title_short | A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities |
| title_sort | blockade of igf signaling sensitizes human ovarian cancer cells to the anthelmintic niclosamide induced anti proliferative and anticancer activities |
| topic | Cancer pathways Cell signaling Synergistic effect Cancer therapy IGF signaling IGF-1R Ovarian cancer Drug repurposing Niclosamide |
| url | http://prod.karger.com/Article/FullText/447797 |
| work_keys_str_mv | AT youlindeng ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT zhongliangwang ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT fuguizhang ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT minqiao ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT zhengjianyan ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT qiangwei ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT jingwang ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT haoliu ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT jiamingfan ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT yulongzou ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT junyiliao ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT xuehu ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT liqunchen ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT xinyiyu ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT rexchaydon ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT huehluu ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT hongboqi ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT tongchuanhe ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT junhuizhang ablockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT youlindeng blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT zhongliangwang blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT fuguizhang blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT minqiao blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT zhengjianyan blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT qiangwei blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT jingwang blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT haoliu blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT jiamingfan blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT yulongzou blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT junyiliao blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT xuehu blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT liqunchen blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT xinyiyu blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT rexchaydon blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT huehluu blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT hongboqi blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT tongchuanhe blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities AT junhuizhang blockadeofigfsignalingsensitizeshumanovariancancercellstotheanthelminticniclosamideinducedantiproliferativeandanticanceractivities |