Suppression of SESN1 reduces cisplatin and hyperthermia resistance through increasing reactive oxygen species (ROS) in human maxillary cancer cells.
INTRODUCTION
Cisplatin is used as a standard chemotherapeutic agent for head and neck cancer treatment. However, some head and neck cancers have cisplatin resistance, leading to difficulty in treatment and poor prognosis. Overcoming cisplatin resistance remains an important strategy to improve prognoses for head and neck cancer patients.


OBJECTIVE
Elucidation of the mechanisms underlying cisplatin resistance can suggest novel targets to enhance the anticancer effects of cisplatin for treating head and neck cancers.


MATERIAL AND METHODS
We used a cisplatin-resistant human maxillary cancer cell line, IMC-3CR to analyse the cisplatin resistance mechanisms. Cisplatin-induced genes were analysed in IMC-3CR cells using PCR array. Among the genes with expression increased by cisplatin, we specifically examined SESN1. SESN family reportedly regenerates peroxiredoxin and suppresses oxidative DNA injury by reactive oxygen species (ROS), which can be induced by chemotherapeutic agents such as cisplatin, radiation, and hyperthermia. The function of SESN1 in cisplatin resistance and ROS generation were analysed using specific RNAi.


RESULTS
Results show that SESN1 was induced by cisplatin treatment in IMC-3CR cells. Suppression of SESN1 by RNAi induced apoptosis and reduced cell viability through enhancement of ROS after cisplatin treatment. Moreover, suppression of SESN1 enhanced the cell-killing effects of hyperthermia with increased ROS, but did not affect the cell-killing effects of radiation.


CONCLUSIONS
This study demonstrated the participation of SESN1 in cisplatin and hyperthermia resistance of human head and neck cancers. SESN1 is a novel molecular target to overcome cisplatin resistance and hyperthermia resistance and improve head and neck cancer treatment.
['Narita|Norihiko|N|', 'Ito|Yumi|Y|', 'Takabayashi|Tetsuji|T|', 'Okamoto|Masayuki|M|', 'Imoto|Yoshimasa|Y|', 'Ogi|Kazuhiro|K|', 'Tokunaga|Takahiro|T|', 'Matsumoto|Hideki|H|', 'Fujieda|Shigeharu|S|']
D000970:Antineoplastic Agents D017209:Apoptosis D045744:Cell Line, Tumor D002945:Cisplatin D019008:Drug Resistance, Neoplasm D015870:Gene Expression D006360:Heat-Shock Proteins D006801:Humans D006979:Hyperthermia, Induced D008441:Maxillary Neoplasms D034622:RNA Interference D034741:RNA, Small Interfering D017382:Reactive Oxygen Species D014162:Transfection
SESN1 cisplatin hyperthermia resistance ROS Head and neck cancers