Role of P38 in endoplasmic reticulum stress-induced chemoresistance to cisplatin in gastric cancer cells / 中国肿瘤临床

ABSTRACT

Objective:To investigate the mechanism of endoplasmic reticulum (ER) stress-induced chemoresistance to cisplatin in gastric cancer cells. Methods:ER stress models were established in both BGC823 and SGC7901 gastric cancer cells. The expression of GRP78, an ER stress marker, was examined by Western blot analysis. Moreover, whether ER stress can decrease the sensitivity of gastric cancer cells to cisplatin and activate P38 was explored by flow cytometry and Western blot analysis, respectively. Whether ER stress-induced chemoresistance to cisplatin can be abrogated by blocking P38 activity in gastric cancer was also elucidated using flow cytometry. Results:GRP78 protein expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with tunica-mycin (TM) or thapsigargin (TG) for 8, 16, and 24 h (P0.05). Both P38 inhibitors, either SB203580 or PD169316, can inhibit the activation of P38. The inhibition of P38 activity can overcome ER stress-induced chemoresistance to cisplatin in gastric cancer cells (P<0.05). Con-clusionER stress can trigger the chemoresistance to cisplatin by activating P38 in gastric cancer cells.