Inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592238
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kagoshima University
• Principal Investigator: KAWABATA Naoya 鹿児島大学, 医歯(薬)学総合研究科, 客員研究員 (60626836)
• Co-Investigator(Kenkyū-buntansha): KOMIYA Setsuro 鹿児島大学, 大学院医歯学総合研究科, 教授 (30178371) ; SETOGUCHI Takao 鹿児島大学, 大学院医歯学総合研究科, 特任准教授 (40423727) ; NAGANO Satoshi 鹿児島大学医学部, 歯学部附属病院, 講師 (50373139) ; ABEMATSU Masahiko 鹿児島大学医学部, 歯学部附属病院, 助教 (70448190) ; TANABE Fumito 鹿児島大学医学部, 歯学部附属病院, 助教 (90619199)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 横紋筋肉腫 / Hedgehog / GLI2 / 骨肉腫

Outline of Final Research Achievements

We investigated the expression and function of the Hedgehog pathway. Real-time PCR revealed that human rhabdomyosarcoma cell lines and biopsy specimens overexpressed the following genes: Sonic hedgehog, Indian hedgehog, Desert hedgehog, PTCH1, SMO, GLI1, GLI2 and ULK3. Immunohistochemistry revealed that rhabdomyosarcoma cell lines and biopsy specimens expressed SMO and GLI2. Inhibition of SMO by cyclopamine slowed the growth of human rhabdomyosarcoma cell lines. Similarly, inhibition of GLI by GANT61 slowed the growth of human rhabdomyosarcoma cell lines. Inhibition of cell proliferation and apoptotic cell death together prevented the growth of rhabdomyosarcoma cells by cyclopamine and GANT61 treatment. In addition, knockdown of GLI2 inhibited invasion of osteosarcoma cell and decreased lung metastasis of osteosarcomas. Our findings suggest that inhibition of the Hedgehog pathway may be a useful approach for treating rhabdomyosarcoma and osteosarcoma patients.

Free Research Field

骨軟部腫瘍