Effects of alphavbeta6 gene silencing by RNA interference in PANC-1 pancreatic carcinoma cells.
BACKGROUND
Integrin alphavbeta6 is up-regulated in a variety of human carcinomas and plays a crucial role in tumor invasion and metastasis. However, the function of alphavbeta6 in pancreatic carcinoma and its potential role in gemcitabine resistance remain unknown.


METHODS
Small interfering RNA (siRNA) targeting alphavbeta6 was constructed and transfected into PANC-1 cells. Effects of alphavbeta6 knockdown on cell proliferation, invasion, cell cycle progression, apoptosis and chemosensitivity to gemcitabine were investigated.


RESULTS
Expression of alphavbeta6 in PANC-1 cells was markedly suppressed by siRNA. Silencing of alphavbeta6 expression significantly inhibited cell proliferation and invasiveness, resulted in cell cycle arrest, and induced cell apoptosis. More importantly, alphavbeta6 knockdown enhanced chemosensitivity to gemcitabine and increased gemcitabine-induced caspase-mediated apoptosis.


CONCLUSIONS
These findings suggest a novel mechanism by which alphavbeta6 contributes to pancreatic carcinoma progression. The combination of alphavbeta6 silencing and gemcitabine treatment may provide an effective therapeutic strategy for highly resistant pancreatic carcinoma.
Niu
Weibo
W
Department of General Surgery, QiLu Hospital of Shandong University, Jinan 250012, P.R. China. niujun120@yahoo.com.cn
Liu
Xiangqun
X
Zhang
Zhaoyang
Z
Xu
Kesen
K
Chen
Rong
R
Liu
Enyu
E
Wang
Jiayong
J
Peng
Cheng
C
Niu
Jun
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D016195:G2 Phase / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D000093542:Gemcitabine
D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D016023:Integrins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C073878:integrin alphavbeta6; D003841:Deoxycytidine; D053148:Caspase 3; D000093542:Gemcitabine