Basic examination of survivin as therapeutic targets in KRAS-mutant lung adenocarcinoma
Description: Survivin is highly expressed in the majority of malignant tumors. However, little is known about the roles of survivin in KRAS-mutant lung adenocarcinomas. In the present study, we examined 28 KRAS-mutant lung adenocarcinoma tissues and two KRAS-mutant lung adenocarcinoma cell lines, H358 and H441, in order to elucidate the potential of survivin as a therapeutic target. Patients with tumors immunohistochemically positive for survivin (n=18) had poorer outcomes than those with survivin-negative tumors (n=10). In the H358 and H441 cells, survivin knockdown alone induced senescence, not apoptosis. However, the H358 cells and H441 cells in which survivin was silenced, underwent significant apoptosis following combined treatment with ABT-263, a Bcl-2 inhibitor, and trametinib, a MEK inhibitor. Importantly, the triple combination of survivin knockdown with ABT-263 and trametinib treatment, clearly induced cell deathin an in vivo tumor xenograft model.
Amount: ¥3,900,000
Funding type: fellowship
Funder scheme: Grant-in-Aid for Young Scientists (B)
Start date: 2016-04-01
End date: 2018-03-31
Investigator: Toshiyuki SUMI
Institution: Sapporo Medical University
Funded outputs count: 2
Funder award ID: 16K19459
OpenAlex ID: G7497344539