Identification of Sestrin3 Involved in the In vitro Resistance of Colorectal Cancer Cells to Irinotecan

Seung Ho Choi; Hye Kyung Hong; Yong Beom Cho; Woo Yong Lee; Hae Yong Yoo

doi:10.1371/journal.pone.0126830

Identification of Sestrin3 Involved in the In vitro Resistance of Colorectal Cancer Cells to Irinotecan

PLoS One. 2015 May 14;10(5):e0126830. doi: 10.1371/journal.pone.0126830. eCollection 2015.

Authors

Seung Ho Choi¹, Hye Kyung Hong², Yong Beom Cho³, Woo Yong Lee², Hae Yong Yoo¹

Affiliations

¹ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea; Samsung Biomedical Research Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.
² Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
³ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

Irinotecan, an analogue of camptothecin, is frequently used as a single agent or in combination with other anticancer drugs for the treatment of colorectal cancer. However, the drug resistance of tumors is a major obstacle to successful cancer treatment. In this study, we established that cells acquire chronic resistance to irinotecan. We profiled their differential gene expression using microarray. After gene ontology (GO) and KEGG pathway analysis of the microarray data, we specifically investigated whether Sestrin3 could decrease irinotecan resistance. Our results revealed that Sestrin3 enhanced the anticancer effect of irinotecan in vitro in LoVo cells that had acquired resistance to irinotecan. Irinotecan-resistant LoVo cells showed lower reactive oxygen species (ROS) production than their irinotecan-sensitive parental cells. ROS production was increased by Sestrin3 knockdown in irinotecan-resistant LoVo cells. Our results indicate that Sestrin3 might be a good target to develop therapeutics that can help to overcome resistance to irinotecan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Camptothecin / analogs & derivatives*
Camptothecin / pharmacology
Cell Cycle Checkpoints / drug effects
Cell Cycle Checkpoints / genetics
Cell Line, Tumor
Cell Survival / drug effects
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology
Drug Resistance, Neoplasm / drug effects*
HCT116 Cells
Heat-Shock Proteins / antagonists & inhibitors
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism*
Humans
Irinotecan
RNA Interference
RNA, Small Interfering / metabolism
Reactive Oxygen Species / metabolism
Transcriptome / drug effects

Substances

Antineoplastic Agents, Phytogenic
Heat-Shock Proteins
RNA, Small Interfering
Reactive Oxygen Species
SESN3 protein, human
Irinotecan
Camptothecin

Associated data

GEO/GSE59501

Grants and funding

This study was supported by grants from the Korea Health technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3418), the National Research Foundation of Korea (NRF-2013R1A1A2060410) and Samsung Medical Center grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.