Overcoming chemoresistance in esophageal cancer by regulating autophagy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka International Cancer Institute
• Principal Investigator: Miyata Hiroshi 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 副部長 (80362713)
• Co-Investigator(Kenkyū-buntansha): 杉村 啓二郎 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 診療主任 (00571374)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オートファジー / 食道癌 / マイトファジー / 化学療法 / 治療抵抗性

Outline of Final Research Achievements

This study investigated the expression and effects of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in esophageal squamous cell carcinoma (ESCC). Both LC3 and Pink1 were analyzed by immunohistochemistry in 217 ESCC patients. Pink1 expression was significantly higher in patients who underwent chemotherapy than in patients who did not (p = 0.032). High LC3 and Pink1 expression was significantly correlated with poor response to chemotherapy (p = 0.004 and p=0.001). High expression of Pink1, but not LC3, was significantly correlated with a poor prognosis for patients treated with preoperative chemotherapy (p = 0.007). In vitro assays demonstrated that inhibition of autophagy and mitophagy using chloroquine and siPink1, respectively, restored chemosensitivity. Thus, high expression of Pink1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy.

Free Research Field

腫瘍学