cancer-therapy-and-biomarkers-2016

Volume 2, Issue 3(Suppl)

Oncol Cancer Case Rep

ISSN: 2471-8556 an open access journal

Page 47

Notes:

Cancer Therapy & Biomarkers 2016

December 05-07, 2016

conferenceseries

.com

CANCER THERAPY,

BIOMARKERS & CLINICAL RESEARCH

World Congress on

December 05-07, 2016 Philadelphia, USA

Simvastatin induces apoptosis of osteosarcoma cells: A novel potential therapeutic approach

Walied A Kamel,

1,2,7

Eiji Sugihara,

Sayaka Yamaguchi,

Koichi Matsuo,

Akihiro Muto,

Hideyuki Saya,

Takatsune Shimizu

1,2

Keio University, Japan

Osteosarcoma (OS) is the most common, non-hematopoietic, primary malignant bone tumor. Previously, we developed an

OS mouse model by overexpressing c-MYC in bone marrow stromal cells derived from Ink4a/Arf knockout mice. We isolated

highly tumorigenic cells (designated AXT cells) from tumors after serial transplantation. To obtain the novel candidate agents

for OS, we performed drug screening and found that statins strongly suppressed AXT cell growth.

Simvastatin treatment inhibited cell proliferation and induced apoptosis, which was almost fully rescued by the supplement of

mevalonate and geranylgeranyl pyrophosphate but modestly by farnesyl pyrophosphate, suggesting that protein geranylgera-

nylation has a greater impact on OS cell viability.

Simvastatin treatment inactivated RhoA through translocation of RhoA from membrane to cytosol and RhoA-GTP was accu-

mulated by disruption of the interaction between RhoA and Rho-GDI.

As a downstream signaling of RhoA, AMPK-p38MAPK pathway was strongly activated by simvastatin treatment, with AMPK

functioning as an upstream effector of p38MAPK. Inhibition of AMPK or p38MAPK activation rescued apoptosis induced by

simvastatin treatment, indicating that simvastatin exerts antitumor activity in OS via activation of AMPK- p38 MAPK pathway.

Although treatment with simvastatin alone did not inhibit OS tumor growth

in vivo

, its combination with a fat-free diet in-

duced a significant antitumor effect that was further enhanced by metformin administration. These findings suggest that the

activation of AMPK- p38 MAPK pathway by statins become a potential therapeutic option for OS.

Biography

Walied kamel, 32 years old, a PHD student at keio unviersity, school of medicine, Tokyo, Japan.

Walied A Kamel et al., Oncol Cancer Case Rep 2016,2:3(Suppl)