Silencing of argininosuccinate lyase inhibits colorectal cancer formation

Hau Lun Huang, Wei Ching Chen, Hui Ping Hsu, Chien Yu Cho, Yu Hsuan Hung, Chih Yang Wang, Ming Derg Lai

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

摘要

Arginine and nitric oxide (NO) are important mediators of tumorigenesis in various types of cancer. Dysregulation of NO content by argininosuccinate lyase (ASL) has been previously demonstrated to inhibit the proliferation of liver and breast cancer cells. However, the function of ASL in colon cancer is not well defined. The present study aimed to determine the effect of ASL on colon cancer. Western blot analysis indicated that ASL expression was induced by endoplasmic reticulum stress in HCT116 and SW480 colon cancer cells. Additionally, the expression of ASL in colon cancer tissues was enhanced compared with that in the adjacent normal tissues, and the patients with colon cancer with higher ASL expression exhibited poorer survival rates. Transfection of ASL-targeting short hairpin RNA (shRNA) into HCT116 cells inhibited cell proliferation and decreased anchorage-independent growth in a soft agar assay. In addition, when injected subcutaneously into NOD/SCID mice, stable transfectant ASL-downregulated HCT116 cells exhibited decreased in vivo tumorigenic ability. Flow cytometric analysis of cell cycle progression indicated that ASL-targeting shRNA induced G2/M arrest, and western blot analysis showed that the inhibition of ASL was accompanied by cyclin A2 degradation. Furthermore, ASL-targeting shRNA resulted in increased autophagosomes and decreased NO levels. Inhibition of NO by the NO synthase inhibitor L-NMMA significantly reduced cell proliferation and colony formation. In summary, the results of the present study indicated that ASL-targeting shRNA-induced growth inhibition is associated with decreased cyclin A2 expression and NO content in colon cancer.
原文英語
頁(從 - 到)163-170
頁數8
期刊Oncology Reports
37
發行號1
DOIs
出版狀態已發佈 - 一月 1 2017
對外發佈Yes

指紋

Neoplastic Gene Expression Regulation
Xenograft Model Antitumor Assays
Cyclin A2
Argininosuccinate Lyase
Neoplastic Cell Transformation
HCT116 Cells
Cyclin A
Inbred NOD Mouse
SCID Mice
Autophagy
RNA Interference
Tumor Cell Line
Endoplasmic Reticulum
Small Interfering RNA
Arginine
Colorectal Neoplasms
Nitric Oxide
Cell Proliferation
Apoptosis
Colonic Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Huang, H. L., Chen, W. C., Hsu, H. P., Cho, C. Y., Hung, Y. H., Wang, C. Y., & Lai, M. D. (2017). Silencing of argininosuccinate lyase inhibits colorectal cancer formation. Oncology Reports, 37(1), 163-170. https://doi.org/10.3892/or.2016.5221

Silencing of argininosuccinate lyase inhibits colorectal cancer formation. / Huang, Hau Lun; Chen, Wei Ching; Hsu, Hui Ping; Cho, Chien Yu; Hung, Yu Hsuan; Wang, Chih Yang; Lai, Ming Derg.

於: Oncology Reports, 卷 37, 編號 1, 01.01.2017, p. 163-170.

研究成果: 雜誌貢獻文章

Huang, HL, Chen, WC, Hsu, HP, Cho, CY, Hung, YH, Wang, CY & Lai, MD 2017, 'Silencing of argininosuccinate lyase inhibits colorectal cancer formation', Oncology Reports, 卷 37, 編號 1, 頁 163-170. https://doi.org/10.3892/or.2016.5221
Huang, Hau Lun ; Chen, Wei Ching ; Hsu, Hui Ping ; Cho, Chien Yu ; Hung, Yu Hsuan ; Wang, Chih Yang ; Lai, Ming Derg. / Silencing of argininosuccinate lyase inhibits colorectal cancer formation. 於: Oncology Reports. 2017 ; 卷 37, 編號 1. 頁 163-170.
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