GRP78 Up-regulation Leads to Hypersensitization to Cisplatin in A549 Lung Cancer Cells

作者：Ahmad Mohammad^*; Hahn Insu Frank; Chatterjee Satadal

来源：Anticancer Research, 2014, 34(7): 3493-3500.

• Apoptosis
• GRP78
• ER stress
• cisplatin
• c-Jun
• NF-kappa B
• cell cycle

Background: GRP78 is one of the stress proteins linked to different functions in the cell. Previous reports have shown opposing functions of GRP78 in relation to drug resistance/sensitivity. In the current study, we examined the role of GRP78 in cisplatin-treated A549 cells. Materials and Methods: GRP78 was over-expressed in A549 cells with 2-deoxyglucose (2-dG) or tunicamycin (TM) treatments for 48 h and subsequently exposed to cisplatin for 2 h. Viability of these cells was determined at 0, 12, 24, 36 and 48 h afterwards. Results: We showed that A549 cells are hypersensitized to cisplatin following a transient GRP78 up-regulation. This hypersensitization is caused by the activation of JNK pathway and NF-kappa B, leading to early onset of apoptosis. Conclusion: Induction of GRP78 can be used as a potential tool to overcome drug resistance in lung cancer cells.

• 出版日期2014-7