OBJECTIVES: 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.
OBJECTIVES: 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 HSP27expression, we found increase of Snail and ERCC1 with reduction of E-cadherin expressions, while reduction of HSP27expression caused reduction of Snail and ERCC1 but increase of E-cadherin expressions. Downregulation of Snail resulted in the reduction of ERCC1expression 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 HSP27expression and GEM sensitivity of SW1990 cells, which might be realized by regulating E-cadherin and ERCC1 expressions through Snail.
Authors: David R Spigel; Dianna L Shipley; David M Waterhouse; Suzanne F Jones; Patrick J Ward; Kent C Shih; Brian Hemphill; Michael McCleod; Robert C Whorf; Ray D Page; Joseph Stilwill; Tarek Mekhail; Cindy Jacobs; Howard A Burris; John D Hainsworth Journal: Oncologist Date: 2019-08-16
Authors: Andrew H Ko; Patrick B Murphy; James D Peyton; Dianna L Shipley; Ahmed Al-Hazzouri; Francisco A Rodriguez; Mark S Womack; Henry Q Xiong; David M Waterhouse; Margaret A Tempero; Shuangli Guo; Cassie M Lane; Chris Earwood; Laura M DeBusk; Johanna C Bendell Journal: Oncologist Date: 2017-09-21
Authors: Smita Tanpure; Jerusha Boyineini; Manu Gnanamony; Reuben Antony; Karen S Fernández; Jaime Libes; Julian Lin; David Pinson; Pushpa A Joseph; Christopher S Gondi Journal: Oncol Lett Date: 2017-04-24 Impact factor: 2.967