Synergistic anti-proliferative effects of mTOR and MEK inhibitors in high-grade chondrosarcoma cell line OUMS-27
| Autor: | Singo Fukumoto, Masashi Neo, Kiyoto Kanbara |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Histology Cell Survival MAP Kinase Signaling System Blotting Western Antineoplastic Agents 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Adjuvant therapy medicine Animals Humans Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation biology Chemistry Cell growth MEK inhibitor TOR Serine-Threonine Kinases Cell Cycle Drug Synergism Cell Biology General Medicine medicine.disease Flow Cytometry 030104 developmental biology 030220 oncology & carcinogenesis Mitogen-activated protein kinase Cancer research biology.protein Chondrosarcoma Mitogen-Activated Protein Kinases |
| Zdroj: | Acta histochemica. 120(2) |
| ISSN: | 1618-0372 |
| Popis: | Chondrosarcoma is a malignant bone tumor that produces cartilaginous neoplastic tissue. Owing to the absence of an effective adjuvant therapy, high-grade chondrosarcoma has a poor prognosis. Therefore, it is important to develop an effective adjuvant therapy to prevent the recurrence and metastasis. Mammalian target of rapamycin (mTOR), a central regulator of cell growth, metabolism, proliferation, and survival, is considered an important target for anticancer drug development. The mitogen activated protein kinase (MAPK) pathway is another highly implicated cellular pathway in cancer and is thought to have compensatory effects in response to the inhibition of the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. We investigated the mechanism of anti-proliferative effect of the mTOR inhibitor rapamycin and MAPK/ERK (MEK) inhibitor PD 0325901, and the combined effect of rapamycin and PD 0325901 on human chondrosarcoma cell line (OUMS-27). Combination therapy with rapamycin and PD 0325901 showed a stronger anti-proliferative effect on OUMS-27 cells than rapamycin monotherapy. We confirmed that the dual inhibition of the PI3K/Akt/mTOR and RAF/MEK/ERK signaling pathways had synergistic anti-proliferative effects in OUMS-27. Our results suggest that combination therapy of mTOR and MEK inhibitor could be an effective therapeutic approach against chondrosarcoma. |
| Databáze: | OpenAIRE |
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