Chemosensitivity to 5-FU was evaluated by both cell proliferation assay and apoptosis
assay. Results: Dramatically inhibited cell proliferation and increased apoptosis were indentified in FU, CUR and FU+CUR compared with Ctrl, but FU+CUR showed the most significant changes. This result suggested that curcumin enhanced chemosensitivity of 5-FU against gastric cancer cells. Mechanically, FU+CUR exhibited the most activation status of PERK signaling pathway than FU and CUR, even in which PERK signaling pathway was also activated. This result indicated that activation of PERK signaling pathway was one of the possible mechanisms in curcumin- enhanced chmosensitivity to 5-FU against gastric cancer cells. Conclusion: Curcumin exerts anticancer activity and chemosensitivity to 5-FU by activating PERK signaling pathway. BMS354825 Key Word(s): 1. PERK; 2. Curcumin; 3. Chemosensitivity; Presenting Author: XIN XU Additional Authors: ZHONGWEI LIU, KUNLUN CHEN, YING LIU, JINKAI XU, JIE LI, JIE WU, YI YANG, JIANGYI CAI Corresponding
FDA-approved Drug Library chemical structure Author: XIN XU Affiliations: The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University; Xi’an Aerospace General Hospital Objective: Original studies have shown that trastuzumab improved overall survival rate in patients with advanced gastric cancer. However, a relatively high trastuzumab resistance for rate was reported in several studies. This study was aimed to elucidate the possible mechanism of trastuzumab resistance in gastric cancer cells. Methods: Trastuzumab
was used to incubate gastric carcinoma cell line MKN45 and NCI-N87. Western blotting was applied to evaluate the phosphorylation of PERK (protein kinase RNA – like ER kinase) in each cell line. Then a PERK gene specific siRNA was transfected into gastric cancer cells. RNA interference was examined by RT-PCR. Drug resistance against trastuzumab was assessed by MTT assay. Results: Gastric cancer cell line MKN45 was found resistant to trastuzumab rather than NCI-N87. The expression of phosphorylated PERK, which is the active form of PERK, increased dramatically in NCI-N87 cells than in MKN45 cells. After knockdown PERK gene by RNAi, NCI-87 exhibited drug resistant behavior against trastuzumab. These results indicated that trastuzumab’s anti- proliferation signaling transduction relied on activation of PERK. Low expression or loss of PERK made gastric cells resistant to trastuzumab. Conclusion: Deficiency of PERK plays an important role in trastuzumab resistance in gastric cancer. Key Word(s): 1. PERK; 2. Trastuzumab; 3.