Simvastatin induces pyroptosis via ROS/caspase-1/GSDMD pathway in colon cancer

被引：31

作者：

Xie, Wei ^{[1
,2
,3
,4
]}

Peng, Mingjing ^{[5
,6
]}

Liu, Ying ^{[7
,8
]}

Zhang, Bocheng ^{[1
,2
,7
,8
]}

Yi, Liang ^{[7
,8
]}

Long, Ying ^{[1
,2
,7
,8
]}

机构：

[1] Cent South Univ, Hunan Canc Hosp, Translat Med Ctr, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China

[2] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Translat Med Ctr, Changsha 410013, Hunan, Peoples R China

[3] Cent South Univ, Hunan Canc Hosp, Xiangya Sch Med, Dept Hepatobiliary Surg, Changsha 410013, Hunan, Peoples R China

[4] Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Dept Hepatobiliary Surg, Changsha 410013, Hunan, Peoples R China

[5] Cent South Univ, Hunan Canc Hosp, Xiangya Sch Med, Cent Lab, Changsha 410013, Hunan, Peoples R China

[6] Cent South Univ, Xiangya Sch Med, Cent Lab, Affiliated Canc Hosp, Changsha 410013, Hunan, Peoples R China

[7] Xiangya Sch Med, Hunan Canc Hosp, Hunan Prov Clin Res Ctr Oncoplast Surg, Changsha 410013, Hunan, Peoples R China

[8] Xiangya Sch Med, Affiliated Canc Hosp, Hunan Prov Clin Res Ctr Oncoplast Surg, Changsha 410013, Hunan, Peoples R China

来源：

CELL COMMUNICATION AND SIGNALING | 2023年 / 21卷 / 01期

关键词：

Simvastatin; Caspase-1; Pyroptosis; ROS; Colon cancer; COLORECTAL-CANCER; PROLIFERATION; CELLS; APOPTOSIS;

D O I：

10.1186/s12964-023-01359-y

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

BackgroundThe outcome of patients with colon cancer is still unsatisfied nowadays. Simvastatin is a type of statins with anti-cancer activity, but its effect on colon cancer cells remains unclear. The present study is intended to determine the underlying mechanism of simvastatin in treatment of colon cancer.MethodsThe viability and pyroptosis rate of cells treated and untreated with simvastatin were analysed by CCK-8 and flow cytometry assays, respectively. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production. Levels of pyroptosis markers were detected by western blotting analysis or immunofluorescence staining. Besides, the anticancer properties of simvastatin on colon cancer were further demonstrated using a cell line based xenograft tumor model.ResultsSimvastatin treatment in HCT116 and SW620 induced pyroptosis and suppressed cell proliferation, with changes in the expression level of NLPR3, ASC, cleaved-caspase-1, mature IL-1 beta, IL-18 and GSDMD-N. Moreover, inhibition of caspase-1 and ROS attenuated the effects of simvastatin on cancer cell viability. In addition, it was identified that simvastatin has an anti-tumor effect by down-regulating ROS production and inducing downstream caspase-1 dependent pyroptosis in the subcutaneous transplantation tumors of HCT116 cells in BALB/c nude mice.ConclusionsOur in vitro and in vivo results indicated that simvastatin induced pyroptosis through ROS/caspase-1/GSDMD pathway, thereby serving as a potential agent for colon cancer treatment.7bxpkuYS9tFbFRGefzbb2gVideo AbstractConclusionsOur in vitro and in vivo results indicated that simvastatin induced pyroptosis through ROS/caspase-1/GSDMD pathway, thereby serving as a potential agent for colon cancer treatment.7bxpkuYS9tFbFRGefzbb2gVideo Abstract

引用

页数：10

共 38 条

[1] A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy [J].

Barbalata, Cristina Ioana ;

Porfire, Alina Silvia ;

Sesarman, Alina ;

Rauca, Valentin-Florian ;

Banciu, Manuela ;

Muntean, Dana ;

Stiufiuc, Rares ;

Moldovan, Alin ;

Moldovan, Cristian ;

Tomuta, Ioan .

PHARMACEUTICS, 2021, 13 (10)

[2] Autologous T cell responses to primary human colorectal cancer spheroids are enhanced by ectonucleotidase inhibition [J].

Bonnereau, Julie ;

Courau, Tristan ;

Asesio, Nicolas ;

Salfati, Delphine ;

Bouhidel, Fatiha ;

Corte, Helene ;

Hamoudi, Sarah ;

Hammoudi, Nassim ;

Lavole, Julie ;

Vivier-Chicoteau, Justine ;

Chardiny, Victor ;

Maggiori, Leon ;

Blery, Mathieu ;

Remark, Romain ;

Bonnafous, Cecile ;

Cattan, Pierre ;

Toubert, Antoine ;

Bhat, Purnima ;

Allez, Matthieu ;

Aparicio, Thomas ;

Le Bourhis, Lionel .

GUT, 2023, 72 (04) :699-709

[3] Statin use and cancer risk: a comprehensive review [J].

Boudreau, Denise M. ;

Yu, Onchee ;

Johnson, Jeanene .

EXPERT OPINION ON DRUG SAFETY, 2010, 9 (04) :603-621

[4] Simvastatin and atorvastatin as inhibitors of proliferation and inducers of apoptosis in human cholangiocarcinoma cells [J].

Buranrat, Benjaporn ;

Senggunprai, Laddawan ;

Prawan, Auemduan ;

Kukongviriyapan, Veerapol .

LIFE SCIENCES, 2016, 153 :41-49

[5] Simvastatin rises reactive oxygen species levels and induces senescence in human melanoma cells by activation of p53/p21 pathway [J].

de Lima Barbosa Guterres, Fernanda Augusta ;

Martinez, Glaucia Regina ;

Merlin Rocha, Maria Eliane ;

Brochado Winnischofer, Sheila Maria .

EXPERIMENTAL CELL RESEARCH, 2013, 319 (19) :2977-2988

[6] The potential use of simvastatin for cancer treatment: A review [J].

Duarte, Jaqueline Aparecida ;

de Barros, Andre Luis Branco ;

Leite, Elaine Amaral .

BIOMEDICINE & PHARMACOTHERAPY, 2021, 141

[7] Colorectal Cancer Organoid-Stroma Biobank Allows Subtype-Specific Assessment of Individualized Therapy Responses [J].

Farin, Henner F. ;

Mosa, Mohammed H. ;

Ndreshkjana, Benardina ;

Grebbin, Britta M. ;

Ritter, Birgit ;

Menche, Constantin ;

Kennel, Kilian B. ;

Ziegler, Paul K. ;

Szabo, Lili ;

Bollrath, Julia ;

Rieder, Dietmar ;

Michels, Birgitta E. ;

Kress, Alena ;

Bozlar, Muege ;

Darvishi, Tahmineh ;

Stier, Sara ;

Kur, Ivan-Maximilano ;

Bankov, Katrin ;

Kesselring, Rebecca ;

Fichtner-Feigl, Stefan ;

Bruene, Bernhard ;

Goetze, Thorsten O. ;

Al-Batran, Salah-Eddin ;

Brandts, Christian H. ;

Bechstein, Wolf O. ;

Wild, Peter J. ;

Weigert, Andreas ;

Mueller, Susanne ;

Knapp, Stefan ;

Trajanoski, Zlatko ;

Greten, Florian R. .

CANCER DISCOVERY, 2023, 13 (10) :2192-2211

[8] A rectal cancer organoid platform to study individual responses to chemoradiation [J].

Ganesh, Karuna ;

Wu, Chao ;

O'Rourke, Kevin P. ;

Szeglin, Bryan C. ;

Zheng, Youyun ;

Sauve, Charles-Etienne Gabriel ;

Adileh, Mohammad ;

Wasserman, Isaac ;

Marco, Michael R. ;

Kim, Amanda S. ;

Shady, Maha ;

Sanchez-Vega, Francisco ;

Karthaus, Wouter R. ;

Won, Helen H. ;

Choi, Seo-Hyun ;

Pelossof, Raphael ;

Barlas, Afsar ;

Ntiamoah, Peter ;

Pappou, Emmanouil ;

Elghouayel, Arthur ;

Strong, James S. ;

Chen, Chin-Tung ;

Harris, Jennifer W. ;

Weiser, Martin R. ;

Nash, Garrett M. ;

Guillem, Jose G. ;

Wei, Iris H. ;

Kolesnick, Richard N. ;

Veeraraghavan, Harini ;

Ortiz, Eduardo J. ;

Petkovska, Iva ;

Cercek, Andrea ;

Manova-Todorova, Katia O. ;

Saltz, Leonard B. ;

Lavery, Jessica A. ;

DeMatteo, Ronald P. ;

Massague, Joan ;

Paty, Philip B. ;

Yaeger, Rona ;

Chen, Xi ;

Patil, Sujata ;

Clevers, Hans ;

Berger, Michael F. ;

Lowe, Scott W. ;

Shia, Jinru ;

Romesser, Paul B. ;

Dow, Lukas E. ;

Garcia-Aguilar, Julio ;

Sawyers, Charles L. ;

Smith, J. Joshua .

NATURE MEDICINE, 2019, 25 (10) :1607-+

[9] 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, fluvastatin, as a novel agent for prophylaxis of renal cancer metastasis [J].

Horiguchi, A ;

Sumitomo, M ;

Asakuma, J ;

Asano, T ;

Hayakawa, M .

CLINICAL CANCER RESEARCH, 2004, 10 (24) :8648-8655

[10] Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment [J].

Hsu, Sheng-Kai ;

Li, Chia-Yang ;

Lin, I-Ling ;

Syue, Wun-Jyun ;

Chen, Yih-Fung ;

Cheng, Kai-Chun ;

Teng, Yen-Ni ;

Lin, Yi-Hsiung ;

Yen, Chia-Hung ;

Chiu, Chien-Chih .

THERANOSTICS, 2021, 11 (18) :8813-8835

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