CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells
被引:41
作者:
Pervaiz, Asim
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German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, GermanyGerman Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
Pervaiz, Asim
[1
]
Ansari, Shariq
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German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, GermanyGerman Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
Ansari, Shariq
[1
]
Berger, Martin R.
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German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, GermanyGerman Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
Berger, Martin R.
[1
]
Adwan, Hassan
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German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, GermanyGerman Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
Adwan, Hassan
[1
]
机构:
[1] German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.
机构:
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
Allen, Samantha J.
;
Crown, Susan E.
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Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
Crown, Susan E.
;
Handel, Tracy M.
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Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
机构:
Barts & London, Queen Marys Med Sch, Canc Res UK Translat Oncol Lab, London EC1M 6BQ, EnglandBarts & London, Queen Marys Med Sch, Canc Res UK Translat Oncol Lab, London EC1M 6BQ, England
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Cambien, Beatrice
;
Richard-Fiardo, Peggy
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Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Richard-Fiardo, Peggy
;
Karimdjee, Babou F.
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机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, France
Clin St Jean, Cagnes Sur Mer, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Karimdjee, Babou F.
;
Martini, Violette
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h-index: 0
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Martini, Violette
;
Ferrua, Bernard
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Fac Med Nice, INSERM, U895, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Ferrua, Bernard
;
Pitard, Bruno
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机构:
INSERM, U915, Nantes, France
In Cell Art, Nantes, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Pitard, Bruno
;
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Schmid-Antomarchi, Heidy
;
Schmid-Alliana, Annie
论文数: 0引用数: 0
h-index: 0
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chang, Li-Yuan
;
Lin, Yung-Chang
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机构:
Chang Gung Univ, Coll Med, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Lin, Yung-Chang
;
Mahalingam, Jayashri
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Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Mahalingam, Jayashri
;
Huang, Ching-Tai
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机构:
Chang Gung Univ, Coll Med, Tao Yuan, Taiwan
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Infect Dis, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Huang, Ching-Tai
;
Chen, Ten-Wen
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Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chen, Ten-Wen
;
Kang, Chiao-Wen
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机构:
Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Kang, Chiao-Wen
;
Peng, Hui-Min
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机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Peng, Hui-Min
;
Chu, Yu-Yi
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Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chu, Yu-Yi
;
Chiang, Jy-Ming
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Chang Gung Mem Hosp, Lin Kou Med Ctr, Colorectal Surg Sect, Dept Surg, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chiang, Jy-Ming
;
Dutta, Avijit
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Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Infect Dis, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Dutta, Avijit
;
Day, Yuan-Ji
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机构:
Chang Gung Univ, Coll Med, Tao Yuan, Taiwan
Chang Gung Mem Hosp, Lin Kou Med Ctr, Grad Inst Clin Med Sci, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Day, Yuan-Ji
;
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Chen, Tse-Ching
;
Yeh, Chau-Ting
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan, Taiwan
Chang Gung Univ, Coll Med, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
机构:
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
Allen, Samantha J.
;
Crown, Susan E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
Crown, Susan E.
;
Handel, Tracy M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
机构:
Barts & London, Queen Marys Med Sch, Canc Res UK Translat Oncol Lab, London EC1M 6BQ, EnglandBarts & London, Queen Marys Med Sch, Canc Res UK Translat Oncol Lab, London EC1M 6BQ, England
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Cambien, Beatrice
;
Richard-Fiardo, Peggy
论文数: 0引用数: 0
h-index: 0
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Richard-Fiardo, Peggy
;
Karimdjee, Babou F.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, France
Clin St Jean, Cagnes Sur Mer, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Karimdjee, Babou F.
;
Martini, Violette
论文数: 0引用数: 0
h-index: 0
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Martini, Violette
;
Ferrua, Bernard
论文数: 0引用数: 0
h-index: 0
机构:
Fac Med Nice, INSERM, U895, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Ferrua, Bernard
;
Pitard, Bruno
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, U915, Nantes, France
In Cell Art, Nantes, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
Pitard, Bruno
;
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机构:
Schmid-Antomarchi, Heidy
;
Schmid-Alliana, Annie
论文数: 0引用数: 0
h-index: 0
机构:
Univ Nice Sophia Antipolis, UFR Med, Nice, France
Fac Med Nice, INSERM, UMR 576, F-06034 Nice, FranceUniv Nice Sophia Antipolis, UFR Med, Nice, France
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chang, Li-Yuan
;
Lin, Yung-Chang
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Univ, Coll Med, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Lin, Yung-Chang
;
Mahalingam, Jayashri
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Mahalingam, Jayashri
;
Huang, Ching-Tai
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Univ, Coll Med, Tao Yuan, Taiwan
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Infect Dis, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Huang, Ching-Tai
;
Chen, Ten-Wen
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chen, Ten-Wen
;
Kang, Chiao-Wen
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Kang, Chiao-Wen
;
Peng, Hui-Min
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Peng, Hui-Min
;
Chu, Yu-Yi
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chu, Yu-Yi
;
Chiang, Jy-Ming
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Colorectal Surg Sect, Dept Surg, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chiang, Jy-Ming
;
Dutta, Avijit
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Infect Dis, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Dutta, Avijit
;
Day, Yuan-Ji
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Univ, Coll Med, Tao Yuan, Taiwan
Chang Gung Mem Hosp, Lin Kou Med Ctr, Grad Inst Clin Med Sci, Tao Yuan 333, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Day, Yuan-Ji
;
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机构:
Chen, Tse-Ching
;
Yeh, Chau-Ting
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan
Chang Gung Univ, Grad Inst Biomed Sci, Tao Yuan, Taiwan
Chang Gung Univ, Coll Med, Tao Yuan, TaiwanChang Gung Mem Hosp, Lin Kou Med Ctr, Dept Hepatogastroenterol, Tao Yuan 333, Taiwan