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Anticancer Drugs at Low Concentrations Upregulate the Activity of Natural Killer Cell
Biomed Sci Letters 2023;29:178-183
Published online September 30, 2023;  https://doi.org/10.15616/BSL.2023.29.3.178
© 2023 The Korean Society For Biomedical Laboratory Sciences.

Hyeokjin Kwon*, Myeongguk Jeong*, Yeeun Kim* and Go-Eun Choi†,**

Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Correspondence to: Eun Choi. Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea.
Tel: +82-51-510-0563, Fax: +82-51-510-0568, e-mail: gechoi@cup.ac.kr
*Graduate student, **Professor.
Received August 22, 2023; Revised September 12, 2023; Accepted September 13, 2023.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of nonkilling (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.
Keywords : Natural Killer cells, Anticancer drug, Activity, Upregulate, CD107a
꽌 濡

븫 21꽭湲 쁽옱 紐⑤뱺 援媛뿉꽌 궗留앹쓽 二쇱슂 썝씤씠硫, 븫 諛쒕퀝瑜좉낵 궗留앸쪧 쟾 꽭怨꾩쟻쑝濡 鍮좊Ⅴ寃 利앷븯怨 엳떎(Bray et al., 2018). 븫 닔硫 옣븷 떊泥 솢룞쓽 옣븷瑜 珥덈옒븯뿬 궣쓽 吏덉쓣 븯떆궓떎(ROBINSON, 1992). 븫쓽 移섎즺踰뺤 諛⑹궗꽑 슂踰, 솕븰 슂踰 諛 닔닠 벑쓽 떎뼇븳 쑀삎쓽 諛⑸쾿씠 엳떎. 븯吏留 씠윭븳 移섎즺踰뺣뱾 遺옉슜쓣 珥덈옒븷 닔 엳떎(Tan et al., 2019). 솗씤맂 二쇱슂 떊泥댁쟻 遺옉슜 援ы넗, 硫붿뒪爰쇱, 깉紐④ 엳쑝硫, 鍮꾩떊泥댁쟻 遺옉슜 遺덉븞, 뵾濡, 떇슃븯, 넻利, 뒪듃젅뒪, 닔硫 옣븷, 泥⑤떒怨듯룷利, 븰뒿, 湲곗뼲, 二쇱쓽젰 벑 떊寃쎌씤吏 寃고븿쓣 珥덈옒븯뒗 寃쎌슦媛 엳떎(Coates et al., 1983; Schirrmacher, 2019).

理쒓렐 湲곗〈 빆븫 移섎즺踰뺤쓣 蹂댁셿븷 닔 엳뒗 諛⑸쾿쑝濡 옄뿰궡빐꽭룷 湲곕컲쓽 硫댁뿭 移섎즺媛 二쇰ぉ諛쏄퀬 엳떎(Lorenzo-Herrero et al., 2018). 옄뿰궡빐꽭룷뒗 諛붿씠윭뒪뿉 媛먯뿼릺怨 븙꽦쑝濡 蹂삎맂 꽭룷뿉 븳 泥 踰덉㎏ 諛⑹뼱꽑쑝濡 꽑泥 硫댁뿭 泥닿퀎 쟻쓳 硫댁뿭 泥닿퀎瑜 뿰寃고븳떎(Khakoo et al., 2004). 옄뿰궡빐꽭룷뒗 궗쟾 솢꽦솕 뾾씠 몴쟻 꽭룷瑜 젣嫄고븯怨 꽭룷룆꽦 솢꽦 뼲젣 諛 솢꽦솕 몴硫 닔슜泥댁쓽 洹좏삎 옟엺 떊샇뿉 쓽빐 議곗젅맂떎(Smyth et al., 2005; Lanier, 2008). 몴쟻 꽭룷쓽 議곌린 궗硫 硫붿빱땲利섏 interferon gamma (IFN-款) 諛 tumor necrosis factor alpha (TNF-慣) 媛숈 硫댁뿭 議곗젅 궗씠넗移댁씤쓽 諛⑹텧쓣 湲곕컲쑝濡(Mart챠n-Fontecha et al., 2004; Vivier et al., 2011) Caspase 쓽議댁꽦 꽭룷 궗硫멸낵 granzyme A B, 꽭룷룆꽦 怨쇰┰쓽 遺꾨퉬瑜 쑀룄븯뒗 granulysin 삉뒗 perforin쑝濡 援ъ꽦맂 꽭룷 궗硫 닔슜泥 由ш컙뱶 寃고빀븳떎(Srivastava et al., 2008; Kwon et al., 2016; Morvan and Lanier, 2016). Fas 由ш컙뱶 諛 TNF 愿젴 꽭룷 궗硫 쑀룄 由ш컙뱶(TRAIL) 媛숈 醫낆뼇 愿댁궗 씤옄(TNF) 怨꾩뿴뿉 냽븯뒗 궗硫 쑀룄 由ш컙뱶쓽 꽭룷 몴硫댁뿉꽌쓽 諛쒗쁽룄 꽭룷留됱쓽 솢꽦솕瑜 쑀룄븳떎. 삉븳 몴쟻 꽭룷뿉꽌 궗硫 닔슜泥(DR), 利 Fas, DR4 (TRAIL-RI) 諛 DR5 (TRAIL-RII)뿉 븳 寃고빀쓣 넻빐 Caspase enzymatic cascade쓽 솢꽦솕瑜 쑀룄븳떎(Wallin et al., 2003; Smyth et al., 2005). 솕븰 슂踰뺤쓽 二쇱슂 紐⑺몴뒗 醫낆뼇 꽭룷쓽 궗硫몄씠떎. 꽭룷룆꽦 빟臾쇱 떎뼇븳 諛⑹떇쑝濡 醫낆뼇 꽭룷瑜 二쎌씠怨 洹몄뿉 뵲씪 닕二 硫댁뿭 泥닿퀎瑜 議곗젅븳떎(Fridman et al., 2011). 뵲씪꽌 빆븫 移섎즺瑜 넻빐 硫댁뿭 移⑥쑄 臾쇱쓽 援ъ꽦쓣 蹂寃쏀븯뿬 븫 젣嫄곗뿉 룄씠 맆 닔 엳떎(Lake and Robinson, 2005). 떎뼇븳 쑀삎쓽 빟臾쇱쓽 뒪듃젅뒪 쑀諛쒖 븫꽭룷뿉 븳 옄뿰궡빐꽭룷 솢꽦솕 삉뒗 뼲젣 由ш컙뱶쓽 諛쒗쁽쓣 議곗젅븯뿬 옄뿰궡빐꽭룷뿉 쓽븳 씤떇 諛 젣嫄곗뿉 쁺뼢쓣 以 닔 엳떎(Zingoni et al., 2017). 醫낆뼇 移섎즺 以 셿쟾븳 愿빐瑜 쐞빐꽌뒗 궡씤꽦 빆醫낆뼇 硫댁뿭씠 븘닔쟻씠씪뒗 寃껋쓣 굹궡뒗 닔留롮 뿰援щ줈 엯利앸릺뿀쑝硫, 엯利 寃곌낵 紐뉖챺 빆醫낆뼇 빟臾쇱 슜웾뿉꽌룄 옞옱쟻씤 硫댁뿭議곗젅젣濡 옱寃넗릺뿀떎(Zitvogel et al., 2008; Zitvogel et al., 2011; R Shurin et al., 2012). 怨쇱궛솕 吏吏(Lipid peroxidation) 룞떇臾쇱뿉 엳뼱꽌 옄꽭븯寃 뿰援щ맂 硫붿빱땲利섏씠떎. 씠 怨쇱젙뿉 쓽빐 留 吏吏덉씠 뙆愿대릺怨 怨쇱궛솕 吏吏덇낵 Isoprostane, Malondialdehyde (MDA), 4-Hydroxynonenal (4-HNE) 媛숈 臾쇱쭏쓣 痢≪젙븿쑝濡쒖뜥 궛솕 뒪듃젅뒪쓽 젙룄瑜 븣 닔 엳떎(Gawe흢 et al., 2004; Lee et al., 2012).

븫꽭룷瑜 二쎌씠怨 룞떆뿉 닕二 빆醫낆뼇 硫댁뿭쓣 쑀吏븯룄濡 怨좎븞맂 移섎즺踰뺤 留ㅻ젰쟻씤 쟾왂씠떎. 궗슜릺뒗 빟臾쇨낵 슜웾뿉 뵲씪 뿬윭 솕븰슂踰뺤젣媛 꽭룷 궗硫몄쓣 넻빐 DNA 넀긽 諛 븫꽭룷 궗硫몄쓣 쑀諛쒗븳떎. 뒪듃젅뒪 쑀諛 硫댁뿭옄洹 떒諛깆쭏 以 옄뿰궡빐꽭룷 솢꽦솕 諛 뼲젣 由ш컙뱶 醫낆뼇 꽭룷 궗硫 닔슜泥댁쓽 諛쒗쁽 닔以 蹂솕뒗 옄뿰궡빐꽭룷瑜 鍮꾨’븳 꽑泥쒖꽦 硫댁뿭 슚怨 씤옄뿉 쓽븳 寃異 諛 젣嫄곗뿉 以묒슂븳 뿭븷쓣 븳떎(Abel et al., 2018; Kumar, 2018; Wu et al., 2020).

빆븫젣 Cisplatin 븫 移섎즺뿉 꼸由 궗슜릺뒗 솕븰슂踰뺤젣씠떎. 怨좏솚븫, 궃냼븫, 몢寃쎈븫, 옣븫 諛 룓븫뿉 빐 긽떦븳 빆醫낆뼇 솢꽦쓣 굹궦떎(Kartalou and Essigmann, 2001).

Cisplatin 뿬윭 硫붿빱땲利섏쓣 넻빐 빆븫 슚怨쇰 諛쒗쐶븯吏留, 洹 以 늿뿉 쓣뒗 옉슜 諛⑹떇 DNA 넀긽 諛섏쓳쓽 솢꽦솕 誘명넗肄섎뱶由ъ븘 꽭룷 궗硫몄쓽 쑀룄뿉 뮘뵲瑜 DNA 蹂묐쓽 깮꽑怨 愿젴씠 엳떎(Galluzzi et al., 2012). 뵲씪꽌 蹂 뿰援ъ뿉꽌뒗 븫 移섎즺뿉 꼸由 궗슜릺뒗 빆븫젣 Cisplatin쓣 궗슜븯뿬 옄뿰궡빐꽭룷쓽 깮議댁쑉쓣 솗씤븯怨 怨좊냽룄 냽룄뿉 뵲瑜 궛솕 뒪듃젅뒪瑜 痢≪젙븯뿬, 븫꽭룷뿉 븳 옄뿰궡빐꽭룷쓽 솢꽦솕瑜 솗씤븯怨좎옄 븳떎.

옱猷 諛 諛⑸쾿

꽭룷二 諛 諛곗뼇

K-562 (ATCC CCL-243TM) 꽭룷二쇰뒗 37꼦, 5% CO2쓽 incubator뿉꽌 諛곗뼇릺뿀쑝硫, 궗슜맂 諛곗뒗 10% Fetal Bovine Serum (GIBCO, Paisley, UK), 100 U/mL penicillin-100 關g/mL streptomycin (GIBCO, Paisley, UK)씠 샎빀맂 RPMI-1640 諛곗 (GIBCO, Paisley, UK)瑜 궗슜뻽떎.

NK-92 (ATCC CCL-2407) 꽭룷二쇰뒗 K-562 꽭룷 룞씪븳 諛곗뼇 議곌굔뿉꽌 諛곗뼇릺뿀쑝硫, 궗슜맂 諛곗뒗 12.5% Fetal Bovine Serum (GIBCO, Paisley, UK), 12.5% Horse Serum (Sigma-aldrich, USA), 100 U/mL penicillin-100 關g/mL streptomycin (GIBCO, Paisley, UK), 200 U/mL IL-2 (PeproTech, USA)媛 샎빀맂 MEM-慣 諛곗(GIBCO, Paisley, UK)瑜 궗슜뻽떎.

꽭룷 깮議댁쑉 遺꾩꽍

빆븫젣 Cisplatin쓽 꽭룷 깮議댁쑉 諛 룆꽦쓣 룊媛븯湲 쐞빐 Cell Counting Kit-8 (Dojindo, Japanese)瑜 궗슜뻽떎. NK-92 꽭룷瑜 96-well plate쓽 媛 well뿉 2 횞 105 cell/mL뵫 遺꾩<븯뿬 MEM-慣 諛곗뿉꽌 24떆媛 룞븞 37꼦, 5% CO2媛 쑀吏릺뒗 incubator뿉 諛곗뼇뻽떎.

洹 썑 Cisplatin쓣 10, 30, 100, 300, 1,000, 3,000 ng/mL 냽룄뿉 留욊쾶 諛곗뿉 씗꽍븯뿬 incubator뿉 24떆媛 諛곗뼇뻽떎. 꽭룷 깮議댁쑉 痢≪젙 Kit 젣議곗궗쓽 吏떆뿉 뵲씪 궗슜 諛 遺꾩꽍뻽떎. 씉愿묐룄 痢≪젙 VarioskanTM LUX (Thermo Fisher Scientific, US)쓣 궗슜븯뿬 450 nm뿉꽌 痢≪젙뻽떎.

궛솕뒪 듃젅뒪 遺꾩꽍

빆븫젣 Cisplatin뿉 븳 NK-92 꽭룷쓽 궛솕 뒪듃젅뒪 닔以쓣 룊媛븯湲 쐞빐 OxiTecTM TBARS Assay Kit (Biomax, Guri, Korea)瑜 궗슜뻽떎. 6-well plate쓽 媛 well뿉 NK-92 꽭룷瑜 2 횞 106 cell/mL뵫 遺꾩<븯뿬, MEM-慣 諛곗뿉꽌 24떆媛 룞븞 37꼦, 5% CO2媛 쑀吏릺뒗 incubator뿉 諛곗뼇뻽떎. 洹 썑 Cisplatin쓣 30, 300 ng/mL 냽룄뿉 留욊쾶 諛곗뿉 씗꽍븯뿬 incubator뿉 24떆媛 諛곗뼇뻽떎. Malondialdehyde (MDA) 痢≪젙 Kit 젣議곗궗쓽 吏떆뿉 뵲씪 궗슜 諛 遺꾩꽍뻽떎. MDA Thiobarbituric Acid (TBA)쓽 諛섏쓳뿉 쓽빐 삎꽦맂 MDA-TBA adduct뒗 VarioskanTM LUX (Thermo Fisher Scientific, Massachusetts, USA)쓣 궗슜븯뿬 532 nm뿉꽌 痢≪젙뻽떎.

쑀꽭룷 遺꾩꽍쓣 넻븳 NK-92 꽭룷 꽭룷룆꽦 깉怨쇰┰쓽 痢≪젙

U-bottom plate뿉 NK-92瑜 2 횞 106 cell/mL뵫 遺꾩<븳 떎쓬 Cisplatin쓣 30, 300 ng/mL 냽룄뿉 留욊쾶 씗꽍븯怨 37꼦, 5% CO2媛 쑀吏릺뒗 incubator뿉 2떆媛 諛곗뼇. 몴쟻 꽭룷 K-562瑜 1 : 1쓽 Effector : Target 鍮꾩쑉뿉 留욎떠 遺꾩< 썑 2떆媛 諛곗뼇븯뿬 옄洹뱁븯떎. 옄洹 썑 꽭룷瑜 V-bottom plate濡 삷寃 630 g뿉꽌 5遺 썝떖遺꾨━ 썑 긽痢듭븸쓣 젣嫄고뻽떎. FACS buffer (PBS with 2% FBS) 꽔뼱 꽭泥 諛 썝떖遺꾨━ 썑 긽痢듭븸쓣 젣嫄고뻽떎. 洹 썑 뿼깋쓣 쐞빐 CD56-PE, CD3-PerCP, CD107a-FITC (Becton-Dickinson, Franklin Lakes, USA) 빆泥대 궗슜븯뿬 鍮 李⑤떒 썑 4꼦뿉꽌 1떆媛 뿼깋뻽떎. 뿼깋 썑 2쉶 꽭泥 諛 썝떖遺꾨━븯怨, E-tube뿉 삷寃 쑀꽭룷 遺꾩꽍湲(AccuriTM C6 Plus Flow Cytometer, Becton-Dickinson, Franklin Lakes, USA)瑜 궗슜븯뿬 痢≪젙뻽떎.

넻怨 遺꾩꽍

뜲씠꽣뒗 룊洹 짹 몴以 렪李(S.D)濡 몴쁽뻽쑝硫, 넻怨 遺꾩꽍 Graph prism 8.4.3 one-way ANOVA (graphpad, California, USA) Flowjo 10.8.1 (Becton-Dickinson, Franklin Lakes, USA)쓣 궗슜뻽떎.

寃 怨

꽭룷 깮議댁쑉 遺꾩꽍

NK-92 꽭룷뿉꽌 빆븫젣 Cisplatin뿉 쓽븳 꽭룷 깮議댁쑉쓣 솗씤븯湲 쐞빐 빆븫젣 Cisplatin쓣 10, 30, 100, 300, 1,000, 3,000 ng/mL뵫 遺꾩<븯뿬 24떆媛 諛곗뼇 썑, VarioskanTM LUX (Thermo Fisher Scientific, US)쓣 궗슜븯뿬 450 nm뿉꽌 痢≪젙뻽떎. 洹 寃곌낵 100 ng/mL遺꽣 議곌뎔 鍮 쁽븯寃 꽭룷 깮議댁쑉쓽 媛먯냼瑜 蹂댁떎(Fig. 1). 씠썑 떎뿕 寃곌낵뿉 뵲씪 0, 30, 300 ng/mL 냽룄瑜 꽕젙븯뿬 닔뻾뻽떎.

Fig. 1. The influence of different cisplatin doses on NK-92 cell viability.
Cisplatin concentrations negatively affected the viability of NK-92 cells for 24-hour exposure. The linear dependence between the dose of cisplatin and cell viability is evident. Half of the maximal inhibitory concentration of cisplatin for NK-92 cells was found to be less than 1,000 ng/mL. All data were compared with the control group. The statistical analysis was performed with Graph Prism 8.4.3 one-way ANOVA test.

궛솕 뒪듃젅뒪 遺꾩꽍

MDA뒗 TBA 諛섏쓳븯뿬 MDA-TBA Adduct瑜 삎꽦븳떎. 痢≪젙 寃곌낵(Fig. 2) 議곌뎔 鍮 怨좊냽룄(300 ng/mL)뿉꽌 쑀쓽誘명븯寃 利앷뻽떎(***P = 0.0007). 議곌뎔 鍮 냽룄(30 ng/mL)뿉꽌뒗 쑀쓽誘명븳 李⑥씠媛 뾾떎(ns = 0.2075).

Fig. 2. Oxidative stress of NK-92 cells under low- to high-dose anticancer drug treatment.
MDA assays of NK-92 cells were conducted to evaluate oxidative stress in the cisplatin. The data indicated that cisplatin increased MDA, increasing expression with higher cisplatin concentrations (ns = 0.2075, ***P = 0.0007 versus control). The statistical analysis was performed with Graph Prism 8.4.3 one-way ANOVA nonparametric test.

쑀꽭룷 遺꾩꽍쓣 넻븳 NK-92 꽭룷 꽭룷룆꽦 깉怨쇰┰쓽 痢≪젙

NK-92 꽭룷쓽 꽭룷룆꽦 깉怨쇰┰솕瑜 痢≪젙 寃곌낵(Fig. 3) NK-92 꽭룷쓽 CD107a 諛쒗쁽 젙룄媛 怨좊냽룄蹂대떎 냽룄뿉꽌 CD107a쓽 諛쒗쁽 젙룄媛 뜑 넂寃 利앷븯떎. 듅엳 빆븫젣瑜 닾뿬븯吏 븡뒗 議곌뎔(B)蹂대떎 냽룄뿉꽌 NK-92 꽭룷쓽 꽭룷 몴硫 CD107a 諛쒗쁽 젙룄瑜 利앹쭊븯뒗 寃껋쑝濡 솗씤맂떎.

Fig. 3. CD107a is expressed at high levels on the surface of NK cells following stimulation.
Flow cytometry figures represent the positive, cytotoxic degranulation of NK cells measured by cell surface expression of CD107a on CD3-CD56+ NK cells. (A) no stimulation, (B) stimulation with K562 cells, (C) stimulation with K562 and Cisplatin 30 ng/mL, (D) stimulation with K562 and Cisplatin 300 ng/mL.
怨 李

理쒓렐 湲곗〈 빆븫 移섎즺踰뺤쓣 蹂댁셿븷 닔 엳뒗 諛⑸쾿쑝濡 옄뿰궡빐꽭룷 湲곕컲쓽 硫댁뿭 移섎즺媛 二쇰ぉ諛쏄퀬 엳떎(Lorenzo-Herrero et al., 2018). 옄뿰궡빐꽭룷뒗 븙꽦 꽭룷, 蹂묒썝泥댁뿉 媛먯뿼맂 꽭룷 궗硫몄뿉 以묒슂븳 뿭븷쓣 븯뒗 꽑泥 硫댁뿭쓽 由쇳봽援ъ씠硫 諛붿씠윭뒪뿉 媛먯뿼릺怨 븙꽦쑝濡 蹂삎맂 꽭룷뿉 븳 泥 踰덉㎏ 諛⑹뼱꽑쑝濡 꽑泥 硫댁뿭 泥닿퀎 쟻쓳 硫댁뿭 泥닿퀎瑜 뿰寃고븳떎(Khakoo et al., 2004). 湲곗〈쓽 솕븰 슂踰뺤 珥덇린 醫낆뼇 꽭룷遺꾩뿴뿉 븳 빆利앹떇 삉뒗 꽭룷룆꽦 슚怨쇰 깮꽦븯룄濡 꽕怨꾨릺뿀떎. 醫낆뼇 꽭룷쓽 꽦옣쓣 뼲젣븯怨, 빆醫낆뼇 硫댁뿭쓣 쑀吏븯뒗 移섎즺踰뺤 븫꽭룷 꽦옣쓣 뼲젣븯뒗 뜲 엳뼱 씎誘몃줈슫 쟾왂씠떎(Zitvogel et al., 2011; R Shurin et al., 2012). 궗슜릺뒗 빟臾쇨낵 슜웾뿉 뵲씪 뿬윭 솕븰슂踰뺤젣媛 꽭룷 궗硫, 硫댁뿭썝꽦 꽭룷 궗硫 諛 옄媛 룷떇쓣 넻빐 DNA 넀긽 諛 븫꽭룷 궗硫몄쓣 쑀諛쒗븳떎. 뒪듃젅뒪 쑀諛 硫댁뿭옄洹 떒諛깆쭏 以 옄뿰궡빐꽭룷 솢꽦솕 諛 뼲젣 由ш컙뱶 醫낆뼇 꽭룷 궗硫 닔슜泥 諛쒗쁽쓽 蹂솕뒗 옄뿰궡빐꽭룷瑜 鍮꾨’븳 꽑泥쒖꽦 硫댁뿭 슚怨 씤옄뿉 쓽븳 寃異 諛 젣嫄곗뿉 以묒슂븳 뿭븷쓣 븳떎(Morvan and Lanier, 2016).

뵲씪꽌 蹂 뿰援ъ뿉꽌뒗 씠윭븳 꽭룷룆꽦 由쇳봽援ш 빆븫 솢꽦뿉 湲곗뿬븯뒗 떎뼇븳 쑀삎쓽 빟臾 以 Cisplatin쓣 궗슜븯뿬 옄뿰궡빐꽭룷쓽 깮議댁쑉쓣 솗씤뻽쑝硫, 怨좊냽룄 냽룄뿉 뵲瑜 궛솕 뒪듃젅뒪瑜 痢≪젙븯硫, 븫꽭룷뿉 븳 옄뿰궡빐꽭룷쓽 솢꽦솕瑜 솗씤븯떎.

Water Soluble Tetrazolium Salt씤 WST-8 궗(metabolism)쟻쑝濡 궡븘엳뒗 꽭룷쓽 誘명넗肄섎뱶由ъ븘 쟾옄쟾떖怨꾩뿉 議댁옱븯뒗 깉닔냼슚냼 諛섏쓳빐 삤젋吏깋쓽 닔슜꽦 formazan쓣 깮꽦븳떎. 뵲씪꽌 formazan쓽 깮꽦 궡븘엳뒗 꽭룷 닔 吏곸꽑 鍮꾨愿怨꾨 媛吏꾨떎. CCK-8 궗슜븯뿬 꽭룷 깮議댁쑉쓣 솗씤뻽쑝硫, 洹 寃곌낵 100 ng/mL遺꽣 議곌뎔 鍮 꽭룷 깮議댁쑉씠 쁽븯寃 媛먯냼瑜 蹂댁떎.

怨쇱궛솕 吏吏(Lipid peroxidation) 룞떇臾쇱뿉 엳뼱꽌 옄꽭븯寃 뿰援щ맂 硫붿빱땲利섏씠떎. 씠 怨쇱젙뿉 쓽빐 留 吏吏덉씠 뙆愿대릺怨 怨쇱궛솕 吏吏덇낵 Isoprostane, MDA, 4-HNE 媛숈 臾쇱쭏씠 깮꽦맂떎. 씠뱾 Oxidative stress쓽 몴쟻씤 Biomarker 뿭븷쓣 븳떎(Nam, 2011). MDA뒗 TBA 諛섏쓳븯뿬 MDA-TBA Adduct瑜 삎꽦븳떎. 씠瑜 痢≪젙븿쑝濡쒖뜥 궛솕 뒪듃젅뒪 젙룄瑜 솗씤뻽쑝硫, 洹 寃곌낵 議곌뎔 鍮 怨좊냽룄뿉꽌 궛솕 뒪듃젅뒪媛 쑀쓽誘명븯寃 利앷뻽떎.

寃곕줎쟻쑝濡 빆븫젣 Cisplatin쓽 냽룄뿉 뵲씪 NK-92 꽭룷쓽 깮議댁쑉 諛 궛솕 뒪듃젅뒪 洹몃━怨 CD107a쓽 꽭룷 몴硫 諛쒗쁽뿉 李⑥씠瑜 蹂댁뿬二쇱뿀떎. 議곌뎔 鍮 怨좊냽룄뿉꽌쓽 궛솕 뒪듃젅뒪媛 냽룄쓽 뒪듃젅뒪 諛쒗쁽蹂대떎 쁽븯寃 넂寃 諛쒗쁽맂 寃껋쓣 븣 닔 엳뿀떎. NK-92 꽭룷쓽 솢꽦룄뒗 議곌뎔 鍮 怨좊냽룄뿉꽌쓽 솢꽦룄媛 궙 닔移섎 蹂댁뿬二쇱뿀쑝硫, 냽룄뿉꽌쓽 솢꽦룄뒗 議곌뎔 鍮 넂 닔移섎 蹂댁뿬二쇱뿀떎. 利, 빆븫젣 Cisplatin쓽 냽룄뿉 鍮꾨븯뿬 궛솕 뒪듃젅뒪媛 利앷릺嫄곕굹 媛먯냼븯硫, CD107a 諛쒗쁽 삉븳 쁺뼢쓣 二쇰뒗 寃껋쑝濡 궗猷뚮맂떎.

蹂 뿰援 寃곌낵瑜 諛뷀깢쑝濡 냽룄쓽 빟臾 移섎즺 떆 솚옄쓽 遺옉슜 셿솕 諛 궣쓽 吏 媛쒖꽑 슚怨쇰 湲곕빐蹂 닔 엳떎. 뜑슧씠 떎뼇븳 蹂댁셿泥댁슂踰뺤쓽 슚怨쇱 遺옉슜뿉 븳 異붽 뿰援ш 븘슂븷 寃껋씠떎.

ACKNOWLEDGEMENT

This study was supported by academic research funds from the Catholic University of Pusan in 2021.

CONFLICT OF INTEREST

There is no potential conflict of interest related to this article.

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