Increased chemotherapeutic activity of camptothecin in cancer cells by siRNA-induced silencing of WRN helicase.
Werner syndrome helicase (WRN) participates in a wide range of DNA activities, including replication, double-strand DNA break repair, telomere and retrovirus long terminal repeat maintenance. Mutations of the WRN gene cause Werner syndrome (WS), an autosomal recessive premature ageing disorder associated with various symptoms related to ageing. In this study, we investigated the siRNA that specifically down-regulates WRN expression. WRN silencing increased markedly the chemotherapeutic activity of camptothecin (CPT) on cancer cells in terms of the extent of efficacy and lowering effective drug dosage, accompanied by suppressing recovery from DNA damage caused by CPT. Here, we propose a potential combination therapy of WRN-siRNA and CPT, looking forward to minimizing the inevitable adverse effects associated with cancer chemotherapy.
Futami
Kazunobu
K
GeneCare Research Institute Co., Ltd., Kamakura, Kanagawa, Japan.
Takagi
Motoki
M
Shimamoto
Akira
A
Sugimoto
Masanobu
M
Furuichi
Yasuhiro
Y
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005090:Exodeoxyribonucleases; D020868:Gene Silencing / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal; D034741:RNA, Small Interfering / Q000494:pharmacology*; D053484:RecQ Helicases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000071657:Werner Syndrome Helicase
D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D002166:Camptothecin