The Effects of HSP27 on Gemcitabine-Resistant Pancreatic Cancer Cell Line Through Snail.
OBJECTIVE
To evaluate the regulation mechanism of heat shock protein 27 (HSP27) on gemcitabine (GEM) resistance of pancreatic cancer cell.


METHODS
The expression vectors pEGFP-C1-HSP27 and the vectors of MicroRNA targeting Snail were introduced into GEM-sensitive pancreatic cancer SW1990 cells, and the vectors of small hairpin RNA targeting HSP27 were transfected into SW1990 and GEM-resistant SW1990/GEM cells. The expressions of HSP27, p-HSP27 (Ser82), Snail, ERCC1, and E-cadherin were evaluated by Western blotting. The sensitivity of transfected cells to GEM was detected by CCK-8 assay and Annexin V-FITC apoptosis assay.


RESULTS
As compared to SW1990, SW1990/GEM showed significantly increased expressions of HSP27, p-HSP27, Snail and ERCC1 with decreased expression of E-cadherin. By increasing HSP27 expression, we found increase of Snail and ERCC1 with reduction of E-cadherin expressions, while reduction of HSP27 expression caused reduction of Snail and ERCC1 but increase of E-cadherin expressions. Downregulation of Snail resulted in the reduction of ERCC1 expression and increase of E-cadherin. Furthermore, downregulation of HSP27 or snail caused increased GEM sensitivity of pancreatic cancer cells, and upregulation of HSP27 showed the opposite results.


CONCLUSIONS
There is an inverse correlation between HSP27 expression and GEM sensitivity of SW1990 cells, which might be realized by regulating E-cadherin and ERCC1 expressions through Snail.
From the Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
Song
S
Zhang
Xiao-qi
XQ
Zhang
Shu-ling
SL
Huang
Min
M
Chen
Shan-shan
SS
Shen
Xi-wei
XW
Ding
Ying
Y
Lv
Xiao-ping
XP
Zou
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D015820:Cadherins; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D003841:Deoxycytidine; C071447:ERCC1 protein, human; D004720:Endonucleases; D000093542:Gemcitabine